Scalp Acupuncture Combined with Mouse Nerve Growth Factor Acupoint Injection for Post-Stroke Cognitive Impairment

Scalp Acupuncture Combined with Mouse Nerve Growth Factor Acupoint Injection for Post-Stroke Cognitive Impairment | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Scalp Acupuncture Combined with Mouse Nerve Growth Factor Acupoint Injection for Post-Stroke Cognitive Impairment Huating Zhou¹, Ming Li¹, Yabo Liu², Tian Ma¹, Xianglin Cheng¹ This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9362962/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background Post-stroke cognitive impairment (PSCI) markedly impairs rehabilitation efficacy and quality of life. Safe and effective combination therapies are urgently needed. Methods Eighty-four patients with PSCI were randomly allocated into three groups (n = 28 per group). Group A received conventional cognitive training. Group B received conventional training plus scalp acupuncture. Group C received the treatment of Group B combined with mouse nerve growth factor (mNGF) acupoint injection. All interventions lasted 4 weeks. Results All groups exhibited significant improvements in MoCA, ADL, MBI, and FMA scores after intervention (P < 0.05). Group C achieved the optimal efficacy: the post-treatment MoCA score was 22.4 ± 3.1, which was significantly higher than 18.2 ± 2.8 in Group A and 19.5 ± 3.0 in Group B (P < 0.01). ADL scores in Group C were the lowest, suggesting better independence in activities of daily living. Conclusions Conventional cognitive training improves cognitive function and daily living ability in patients with PSCI. Scalp acupuncture combined with conventional training is more effective than training alone. The triple therapy of conventional training, scalp acupuncture, and mNGF acupoint injection further enhances rehabilitation outcomes, with prominent clinical application value. Post-stroke cognitive impairment Scalp acupuncture Mouse nerve growth factor Acupoint injection Cognitive rehabilitation1 Figures Figure 1 Figure 2 Figure 3 1. Introduction Post-stroke cognitive impairment (PSCI) refers to the decline in cognitive function following a stroke. Stroke, caused by the obstruction or rupture of brain blood vessels, leads to brain tissue damage and typically results in a series of neurological symptoms including motor dysfunction, sensory disturbance, and language disorder. Cognitive impairment involves deficits in thinking, memory, learning, and judgment. Up to 75% of stroke survivors develop cognitive impairment within the first year after the stroke [ 1 – 4 ]. Between 75% and 85% of stroke patients experience varying degrees of cognitive impairment within six months post-stroke [ 5 ]. More and more clinical research indicates that cognitive impairment not only affects the daily living abilities of stroke patients, but also severely hinders their overall recovery [ 6 – 10 ]. roving cognitive function in PSCI patients has become a significant focus for clinicians. In the diagnosis of cognitive impairment, decline is often observed in visuospatial and executive functions, attention, memory, language ability, and orientation [ 11 – 13 ]. Current pharmacotherapy for the treatment of PSCI is largely based on the use of antidepressants that may provide minor or short-term benefits in specific cognitive domains such as verbal and visual memory functions [ 14 ],but the long-term clinical efficacy of the use of antidepressants is rather limited, with associated side effects such as headaches and dizziness, nausea, weight gain, anxiety or restlessness, difficulty sleeping or excessive sleepiness. Therefore, pharmacotherapy is often associated with significant side effects, limiting its long-term clinical utility. In contrast, non-pharmacological interventions, particularly Traditional Chinese Medicine (TCM) modalities, have emerged as promising alternatives for PSCI. Recent clinical evidence suggests that acupuncture-based therapies can effectively modulate neural plasticity and improve cognitive outcomes in stroke patients [ 15 ]. Traditional Chinese medicine (TCM) is a healthcare system largely used over thousands of years in China to prevent, diagnose, and treat disease [ 16 ].It is based on the Chinese philosophy of Yin–Yang, vital energy (Qi), and five elements (metal, wood, water, fire and earth). As part of the ancient practice of TCM, acupuncture consists in inserting needles into the body to stimulate sensory nerves in the skin and muscles. This needling is able to affect the central nervous system and treat different nervous system dysfunctions such as stroke, Parkinson's disease, traumatic brain injury, chronic pain, depression, spinal injury, etc. [ 17 ]. Moreover, acupuncture has been approved by the World Health Organization (WHO) for stroke treatment due to its advantages in managing cerebrovascular diseases, including ischemic stroke [ 18 ].A number of clinical studies have evidenced the efficacy of acupuncture in ameliorating neurological dysfunctions following stroke [ 19 – 20 ].Scalp acupuncture, a specific microsystem acupuncture technique, involves needling on defined scalp zones corresponding to cortical areas. It has been widely used in post-stroke rehabilitation, showing potential in improving cognitive and motor functions [ 21 ].Acupoint injection, also known as pharmacopuncture, is a TCM-based technique that injects small amounts of medication into acupoints, combining the effects of needling stimulation with pharmacological action [ 22 ]. This approach may enhance local bioavailability and reduce systemic side effects. Nerve growth factor (NGF) is a neurotrophic protein which plays a key role in the development and maintenance of the nervous system in mammals [ 23 ]. It is essential for the survival of both sensory and sympathetic neurons, and also helps maintain neuronal function and promotes repair following nerve injury [ 24 ]. It has been shown that NGF can regulate the inflammatory responses [ 25 ],reduce neuronal apoptosis [ 26 ], and improve the functional recovery in the damaged area by promoting angiogenesis [ 27 ] and nerve regeneration [ 28 ]. Clinically, mNGF is mainly used for functional improvements (e.g., cognitive function, sensory, motor functions). Given that acupuncture can modulate neurotrophic factor expression and promote neural plasticity, and NGF directly supports neuronal survival and repair, their combination via acupoint injection may produce synergistic effects on post-stroke cognitive recovery. However, clinical evidence for such combined therapy remains limited. This work aimed to comparatively evaluate the clinical efficacy of scalp acupuncture combined with mNGF acupoint injection in the treatment of post-stroke cognitive impairment (PSCI). Eighty-four stroke patients were randomly divided into three groups which were subjected to conventional cognitive training, conventional treatment plus scalp acupuncture, and conventional training plus scalp acupuncture and mNGF acupoint injection. Various methods including Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL) scale, Fugl-Meyer Assessment (FMA), and modified Barthel Index were used to evaluate the effects of different treatments on the recovery of stroke patients. The results are reported herein in comparison with literature data. 2. Clinical Data Clinical trial registration number:AF/16 − 1.0, Registration date: April 1, 2024 Participant recruitment start date: April 15, 2024 2.1 General Data of Patients From April 2024 to April 2025 ,84 patients with post-stroke cognitive impairment were enrolled from the Department of Rehabilitation Medicine at First People's Hospital of Jingzhou for this study. These 84 patients were randomly divided into three groups: Group A, Group B, and Group C, with 28 patients in each group. Group A was composed of 15 males and 13 females, aged from 45 to 79 years with a mean age of (61.5 ± 3.9) years. Group B was composed of 14 males and 14 females, aged from 43 to 78 years with a mean age of (62.3 ± 4.1) years. Group C was composed of 13 males and 15 females, aged from 44 to 78 years with a mean age of (61.3 ± 4.2) years.The disease course for Group A, Group B, and Group C was 63.5 ± 47.7 days, 63.7 ± 50.0 days, and 64.0 ± 48.4 days, respectively. Among the 84 patients, there were 64 cases of ischemic stroke and 20 cases of hemorrhagic stroke. There were no statistically significant differences in the baseline characteristics among the groups (P > 0.05). There were no statistically significant differences in gender distribution (χ²=0.26, P > 0.05) or stroke type (χ²=0.18, P > 0.05) among the three groups. All outcome assessments were performed by a single blinded attending physician in rehabilitation medicine. Data analysis was performed by an independent statistician who only had access to the collected data, ensuring the authenticity and reliability of the results. 2.2 Diagnostic Criteria The diagnostic criteria are based on the diagnostic criteria for mild cognitive impairment from the "Key Points of Diagnosis for Various Major Cerebrovascular Diseases in China 2019" [ 29 ]. and the "China Stroke Center Report 2020" [ 30 ], both published by the Cerebrovascular Disease Group of the Neurology Branch of the Chinese Medical Association. 2.3 Patient Inclusion Criteria (1) Meet the above diagnostic criteria, have a confirmed history of stroke evidenced by imaging examinations (cranial CT or MRI), and be currently in the recovery phase;(2) Have a disease duration of ≤ 6 months, with other causative factors excluded; have no liver or kidney dysfunction, no bleeding tendency, and no severe cardiovascular disease;(3)Be aged between 18 and 79 years;(4) Have a Montreal Cognitive Assessment (MoCA) score < 26;(5) Have activities of daily living that are normal or mildly impaired, unrelated to motor or sensory symptoms, with an Activities of Daily Living (ADL) scale score between 20 and 60;(6)Have an education level above primary school. 2.4 Patient Exclusion Criteria The exclusion criteria are as follows: (1) Presence of significant visual or hearing impairments; (2) Severe complications of the circulatory or respiratory systems; (3) Diagnosed psychiatric disorders; (4) Incomplete clinical data that cannot be supplemented; (5) Diagnosed malignant tumors or infectious diseases; (6) Poor compliance due to pain sensitivity. 3. Methods 3.1 Group A Patients Based on the cognitive level of the patients, Group A patients were treated in accordance with the recommendations of the China Stroke Center Report 2020 [31]". The one-on-one rehabilitation training adopted appropriate approaches by progressively increasing the training intensity. The rehabilitation exercises included: 1) Orientation training: Patients were asked to describe their home address, the environment around their home, and the current time and date each day. Alternatively, therapists trained patients to recognize their left and right hands, providing simple methods to distinguish them and conducting repetitive training; 2) Memory and thinking skills training: Using number games designed for children aged 0–6 years or scrambled number sequences to train patients' thinking and arithmetic abilities; 3) Reasoning training: Encouraging patients to describe the uses of certain plants, animals, or foods, or to associate them with related items; 4) Memory training: Patients repeatedly viewed patterned images with various colors and were told the names of the pictures. They were then asked to repeatedly name the pictures and their colors, with the difficulty gradually increasing; 5) Language training: Patients were encouraged to read books and newspapers aloud, engage in frequent conversations with family members, and recall and narrate past events [32].These exercises were conducted for patients from Monday to Friday, with each session lasting 45 ± 15 minutes, once a day, for four consecutive weeks. 3.2 Group B Patients In addition to the treatments provided to Group A, scalp acupuncture was applied to Group B patients. The acupoints included: Zhi Nine Needles, Temporal Three Needles, Exercise Area, Sensory Area, Computation Area, Baihui (GV20), Shenting (GV24). Patients were seated, and 0.3 mm×25 mm disposable sterile acupuncture needles were used. The selected acupoints were disinfected according to sterile procedures. The needles were inserted quickly in a parallel fashion into the scalp, reaching the subgaleal layer. Then, the needles were angled at approximately 20° to the scalp surface and manipulated with a twirling technique to elicit Qi. Needles were retained for 1 hour. During the needle retention period, routine cognitive dysfunction training could be conducted. This treatment was performed once daily, Monday through Friday,for 4 consecutive weeks. 3.3 Group C Patients In addition to the treatments provided to Groups A and B, Group C patients received mNGF acupoint injection. 20µg (9000U) of mNGF (manufactured by Wuhan Hiteck Biological Pharma Co., Ltd., National Drug Standard S20060051) was diluted in 2 mL of saline. The acupoints Baihui (GV20), Shenting (GV24), and bilateral Fengchi (GB20) were selected using the bone proportional measurement method. The injection area was carefully disinfected with iodine. The prepared solution was slowly and gently injected into the acupoints at a depth of 0.5–1.0 cm, with each acupoint receiving 0.5 mL of the diluted solution after confirming no blood return. The injection sites were pressed for 1 minute post-injection. This treatment was done once daily on Monday, Wednesday, and Friday for 4 consecutive weeks. 4. Efficacy Observation 4.1 Observation Indicators Four observation indicators were used to evaluate treatment efficacy: the Montreal Cognitive Assessment (MoCA), the Activities of Daily Living Scale (ADL), the Modified Barthel Index (MBI), and the Simplified Fugl-Meyer Motor Function Assessment (FMA). Scores before and after treatment were compared among the three groups to assess patients' cognitive function, daily living ability, basic self-care ability, and limb motor function, respectively. For the MoCA, MBI, and FMA, higher scores indicate better outcomes, whereas for the ADL, a lower score indicates a better outcome. 4.1.1 Primary Observation Indicator Montreal Cognitive Assessment (MoCA) is the primary observation indicator [30].The MoCA includes 7 core cognitive domains: visuospatial/executive functions, naming, attention, language, abstraction, delayed recall, and orientation.It consists of 30 items, with a total score ranging from 0 to 30 points. The total score is categorized into four levels: scores above 26 indicate no cognitive impairment; scores between 19 and 25 indicate mild cognitive impairment; scores between 12 and 18 indicate moderate cognitive impairment; and scores below 12 indicate severe cognitive impairment. 4.1.2 Secondary Observation Indicators (1) Secondary observation indicators include ADL, MBI and FMA[33].The ADL scale assesses basic and instrumental Activities of Daily Living across 20 items [34]. Each item is scored from 1 to 4, with 1 indicating the patient can perform the activity independently, 2 indicating some difficulty, 3 indicating the need for assistance, and 4 indicating the patient cannot perform the activity at all. The total score ranges from 20 to 80, with scores above 23 indicating cognitive impairment. (2) MBI[35] and simplified FMA[36] are used to evaluate the patient's basic self-care ability and limb motor function, respectively. Higher scores indicate better functional recovery. 4.2 Treatment Safety Assessment The safety assessment involved close monitoring for adverse events (e.g., syncope, bent needles, stuck needles, broken needles) in patients of Groups B and C. For Group C in particular, subcutaneous hematomas at injection sites were additionally monitored, with prompt symptomatic treatment administered as required. Adverse events were systematically monitored throughout the entire 4-week intervention period and recorded immediately upon occurrence for subsequent analysis. 5. Statistical Methods All statistical analyses followed rigorous biostatistical principles. Categorical data were presented as frequencies and percentages (n, %) and compared across groups using the chi-square (χ²) test. Continuous data, including scores from the Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL) scale, Modified Barthel Index (MBI), and Fugl-Meyer Assessment (FMA), were first tested for normality and homogeneity of variance. Data conforming to a normal distribution were expressed as mean ± standard deviation (x̄ ± s). Paired-sample t-tests were used for intragroup comparisons of scores before and after treatment. One-way analysis of variance (ANOVA) was performed for intergroup comparisons of baseline and post-treatment scores, with the least significant difference (LSD) post-hoc test applied for multiple pairwise comparisons. A two-tailed P value < 0.05 was considered statistically significant. 6. Results 6.1 Comparison of General Data Among the Three Groups Three patients in Group B dropped out due to pain intolerance, and two patients in Group C dropped out due to hematomas after acupoint injection. Ultimately, a total of 79 patients were included in the statistical analysis: 28 in Group A, 25 in Group B, and 26 in Group C. The mean ages of the three groups were 61.5 ± 3.9, 62.3 ± 4.1, and 61.3 ± 4.2 years, respectively, and the disease courses were 63.5 ± 47.7, 63.7 ± 50.0, and 64.0 ± 48.4 days, respectively. No statistically significant differences were observed in age (F = 0.19, P > 0.05) or disease course (F = 0.02, P > 0.05) among the three groups, indicating good comparability (Fig. 1 ). No serious adverse events were reported during the entire intervention period. Mild adverse events, such as small hematomas at the injection site, were relieved after symptomatic treatment, confirming the acceptable safety and tolerability of the intervention protocols adopted in this study. 6.2 Comparison of MoCA Scores Before and After Treatment Baseline MoCA total scores and subscale scores across the seven cognitive domains were comparable among the three groups, with no statistically significant intergroup differences (F = 0.21, P > 0.05), indicating homogeneous severity of cognitive impairment at study initiation. After 4 weeks of intervention, all groups showed significant within-group improvements in MoCA total and subscale scores (all P < 0.05). Notably, Group C achieved the most robust therapeutic effects, with a post-intervention MoCA total score of 22.4 ± 3.1 that was significantly higher than that of Group B (19.5 ± 3.0) and Group A (18.2 ± 2.8) (F = 6.83, P < 0.01). In terms of cognitive domain-specific changes, Group A showed notable improvements in orientation, naming, abstraction, attention, and visuospatial/executive functions, with a mild elevation in total score and language subscale, and a significant enhancement in delayed recall. Group B presented marginal improvements in total score, naming, delayed recall, and visuospatial/executive functions relative to Group A, with less pronounced gains in orientation and attention, but a marked improvement in abstraction and a significant boost in language ability. For Group C, while improvements in orientation, naming, and attention were comparable to or less pronounced than those in Groups A and B (a trend that warrants further investigation with larger sample sizes to elucidate the underlying mechanisms), the group demonstrated striking elevations in MoCA total score, abstraction, and visuospatial/executive functions. Compared with Group B, Group C also showed a slight improvement in language ability and a prominent enhancement in delayed recall, which highlights the specific efficacy and potential advantages of mNGF in ameliorating memory deficits associated with post-stroke cognitive impairment. 6.3 Comparison of ADL Scores Before and After Treatment Before treatment, no statistically significant differences were found in ADL scores among the three groups at any time point (F = 0.35, P > 0.05), indicating comparability. After the rehabilitation intervention, all groups showed decreases in ADL scores at each time point, and these within-group differences were statistically significant (P < 0.05). Intergroup comparison revealed that Group C had the lowest ADL score (F = 5.92, P 0.05). After the 4-week intervention, all groups showed varying degrees of improvement, with Group C exhibiting more pronounced changes than the other two groups (Fig. 3 ). However, no statistically significant differences were found among the three groups in post-treatment FMA and MBI scores (F_FMA = 1.15, F_MBI = 1.08, both P > 0.05). Although the intergroup comparison did not reach statistical significance, a distinct trend was observed: Group C had the highest mean score increments in both motor and functional assessments compared to Groups A and B, suggesting a potential clinical benefit that may require larger sample sizes to validate. 7. Discussion Post-stroke cognitive impairment (PSCI) stands as one of the most prevalent functional sequelae of stroke, alongside hemiplegia and focal neurological deficits. PSCI presents with heterogeneous clinical manifestations and varying severity, which impairs patients’ environmental perceptual capacity and consequently induces adaptive dysfunction. Approximately one-third of affected individuals predominantly suffer from deficits in memory, visuospatial processing, attention, language, and executive function, with a subset progressing to post-stroke dementia. Notably, the nervous system possesses a robust capacity for structural and functional plasticity; through targeted basic rehabilitation training and cognitive retraining, patients can effectively promote neural network remodeling and cerebral functional reorganization, thus facilitating the recovery of cognitive, mnemonic, and executive functions. Developing personalized intervention regimens tailored to distinct cognitive domains—including memory, comprehension, language, and logical reasoning—can further accelerate cerebral structural remodeling and functional restoration, which is pivotal to the comprehensive rehabilitation of stroke survivors. The combination of cognitive training and scalp acupuncture exerts a synergistic effect in ameliorating post-stroke pathological states such as cerebral hypoperfusion, cerebral tissue ischemia, and hypoxia, thereby mitigating neurodegeneration and cerebral atrophy, as well as delaying the progression of neurological dysfunction [37–39]. In Traditional Chinese Medicine (TCM), cognitive disorders are categorized under the broad spectrum of dementia, a clinical entity highly associated with vascular pathological changes in the central nervous system and widely documented in clinical TCM research [1, 40]. The core TCM tenet holds that the brain serves as the abode of the spirit (shen) and vital qi (Qi), a pivotal region where all Yang meridians converge and the meridional system is densely distributed, forming the anatomical and meridian basis for scalp acupuncture in regulating cerebral functions [2.41]. In his seminal work Correcting Errors in the Forest of Medicine: On the Human Brain, Wang Qingren explicitly challenged the traditional TCM view of cardiac domination of mental activity and stated: "Where do the mind and memory originate and reside? The mind and memory abide in the brain."Similarly, Wang Ang noted in Essentials of Materia Medica that "human memory resides in the brain", "the head is the seat of the spirit", and "therapeutic effects reach the loci where acupuncture points are stimulated", laying a theoretical foundation for scalp acupuncture in the treatment of cerebral disorders [42]. As a classic microsystem acupuncture technique with a long history of clinical application, scalp acupuncture has been validated to target specific cortical corresponding regions of the scalp for needling, and the present study posits that scalp acupuncture at specific acupoints and functional regions—including the Wisdom Nine Needles, Temporal Three Needles, Motor Area, Sensory Area, Baihui (GV20), Shenting (GV24), and Arithmetic Area [43, 44]—exerts a regulatory effect on impaired cerebral cognitive functions by stimulating the meridians and collaterals converging on the head and modulating the circulation of cerebral qi and blood..Here is the polished, high-standard SCI version (concise, academic, logically tight, suitable for TMR / neuroscience journals):can mitigate neuronal injury and facilitate neural repair in lesioned brain regions via activating specific neural pathways. Accumulating evidence has demonstrated that scalp acupuncture upregulates the expression of brain-derived neurotrophic factor (BDNF), a key neurotrophin supporting neuronal growth, survival, and synaptic remodeling, thereby exerting beneficial effects on cognitive recovery after stroke. Furthermore, scalp acupuncture in PSCI management can decrease whole blood viscosity, which in turn promotes the repair and regeneration of impaired cerebral cells and facilitates the reconstruction of short-term memory circuits. Patients in group C received additional mouse nerve growth factor (mNGF) injection at Baihui (GV20), Shenting (GV24), and Fengchi (GB20) acupoints to enhance neural plasticity and remodeling. Following stroke, endogenous cerebral neural remodeling is significantly compromised, accompanied by disrupted neuronal connectivity and synaptic transmission. Notably, most clinical investigations have adopted recombinant human nerve growth factor (rhNGF), while clinical studies investigating the application of mNGF in human subjects remain limited [45–49]. mNGF is one of the crucial bioactive molecules in the nervous system, and its homology with human NGF exceeds 90%. It promotes the growth, development, differentiation, and maturation of central and peripheral neurons, maintains the survival of sympathetic and sensory nerves, and accelerates the repair of nervous system injuries. It can enhance connectivity between neurons and synaptic transmission, thereby improving the reconstruction of neural networks in the brain. It also plays a key role in brain development and the repair and regeneration of the injured nervous system. In this study, mNGF was used to provide the protein molecules necessary for neural growth and development, repair neural damage, and improve cognitive impairment in patients [50]. Acupoint injection of mNGF combines acupuncture and medication. The injection needle stimulates the Baihui, Shenting, and Fengchi acupoints, delivering the drug to these points to stimulate the numerous surrounding nerve receptors. By stimulating acupoints to enhance the transmission function of the meridians, this approach helps regulate patients’ cognitive abilities. Using mNGF to stimulate local tissues at acupoints aids in promoting neural growth, differentiation, and metabolism, accelerating the myelination of nerve fibers. Additionally, it improves microcirculation, facilitating the supply of more oxygen and nutrients to damaged brain areas, thereby enhancing the recovery of cognitive functions [50–53]. This approach also shortens the development and maturation time of neuronal synaptic structures and strengthens the repair of nervous system injuries. Several studies have employed randomized controlled trials to explore various treatments for PSCI. One study combined conventional treatment, cognitive rehabilitation training, and scalp acupuncture, using the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) scoring method [54]. Another study administered mNGF to patients with cerebral infarction alongside conventional medication, showing that NIH Stroke Scale scores were lower, while Mini-Mental State Examination (MMSE) and Fugl-Meyer Assessment (FMA) scores were higher compared to the control group that received only conventional treatment [55].This suggests that mNGF can effectively reduce neurological deficits in acute cerebral infarction patients, improving their cognitive and motor functions. In another study, acute cerebral infarction patients were divided into a short-term mNGF treatment group, a long-term mNGF treatment group, and a conventional treatment group [56].The long-term treatment group showed significantly better improvements in neurological scores, MMSE, and FMA scores compared to the other two groups. The overall efficacy rate of the short-term treatment group did not significantly differ from that of the conventional treatment group, possibly because neuronal repair and the establishment of neural pathways are slow processes, and sustained exogenous NGF supplementation may be more beneficial; short-term treatment effects are very limited. Therefore, mNGF not only promotes the repair of the nervous system in acute cerebral infarction patients but also aids the recovery of motor and cognitive functions, with longer treatment durations yielding better results. Another study used electroacupuncture combined with acupoint injection to treat ischemic cerebral infarction, assessing efficacy through the Neurological Functional Deficit Score (NFDS) and Functional Independence Measure (FIM)[57]. In the present study, the Montreal Cognitive Assessment (MoCA), Activities of Daily Living Scale (ADL), Fugl-Meyer Assessment (FMA), and Modified Barthel Index (MBI) were employed to comprehensively evaluate cognitive function, daily living ability, motor function, and basic self-care capacity in patients with PSCI[58].MoCA, in contrast to ADL, FMA, and MBI, is a more rigorous assessment tool with higher discriminatory power, covering a broader spectrum of cognitive domains including visuospatial executive function, abstraction, and delayed recall [59].By comparison, ADL, FMA, and MBI are characterized by simplicity and ease of clinical operation, with high sensitivity in assessing self-care ability, motor function, and memory-related daily living competence, thus serving as the most commonly used scales for screening functional independence in stroke rehabilitation [60].The combined application of these four standardized scales enabled a multi-dimensional evaluation of PSCI improvement, effectively enhancing the sensitivity, discriminability, and validity of therapeutic effect assessment in this study. The findings of this study strongly corroborate the neuroprotective and cognitive-improving effects of mouse nerve growth factor (mNGF) in stroke patients as reported in previous studies[61, 62].Nevertheless, the improvements in orientation, naming, and attention subdomains in Group C were less pronounced (P 0.05 vs. Group B), suggesting that further investigations with larger sample sizes, long-term versus short-term treatment follow-ups, and analysis of potential confounding or synergistic factors are warranted to elucidate the underlying mechanism. To simplify the intervention protocol and minimize confounding variables, electroacupuncture and acupoint injection of traditional Chinese medicine (TCM) preparations (e.g., Salvia miltiorrhiza injection and Codonopsis pilosula injection) were not adopted in the present study[63, 64].Additionally, as a classic neurotrophic factor, mNGF has been extensively investigated in basic research regarding its physicochemical properties and neuroprotective mechanisms, but clinical application studies focusing on its efficacy in combination with TCM acupuncture for PSCI remain limited. Unlike complex multicomponent TCM preparations, mNGF is a highly purified protein with a specific molecular structure, which ensures the stability and homogeneity of its pharmacological effects in clinical application[65]. Unlike limb hemiplegia with overt motor deficits, PSCI is insidious and easily overlooked in clinical practice, underscoring the necessity of early cognitive assessment and timely intervention [66, 67].Future investigations should enroll larger sample sizes, extend treatment and follow-up durations, and perform dynamic monitoring of cognitive function, daily living ability, and stroke recurrence in PSCI patients. Incorporating more comprehensive post-treatment assessment indicators (e.g., serum neurotrophic factor levels and neuroimaging markers) will enable objective and in-depth evaluation, thereby providing more robust clinical evidence to validate the efficacy and clinical value of scalp acupuncture combined with mNGF acupoint injection for PSCI. 8. Conclusions This study demonstrated that conventional cognitive training effectively improved cognitive function and activities of daily living in patients with post-stroke cognitive impairment (PSCI). Scalp acupuncture combined with conventional training yielded significantly better outcomes than training alone. Notably, the triple intervention of conventional cognitive training, scalp acupuncture, and mouse nerve growth factor (mNGF) acupoint injection further enhanced the rehabilitation efficacy, with superior improvements in MoCA, ADL, MBI, and FMA scores. This combined therapy is safe, well-tolerated, and has high clinical application value for the management of PSCI. Declarations Ethics Approval and Consent to Participate This study was approved by the Ethics Committee of Jingzhou First People's Hospital (IRB Approval Number: AF/16 − 1.0, Date of Approval: April 1, 2024). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. We have obtained informed consent from all participants in this study. To strictly protect patients' personal privacy, we will not submit the individual consent documents of all participants. Only one sample copy of the informed consent form is provided here with the participant's explicit permission for journal review reference. Author Contribution Huating Zhou and Ming Li contributed equally to this work.The specific contributions are as follows:Huating Zhou: Conceptualization, Methodology, Investigation, Formal Analysis, Writing - Original Draft, Visualization.Ming Li: Investigation, Data Curation, Writing - Original Draft, Project Administration.Yabo Liu: Software, Validation, Resources, Writing - Review & Editing.Tian Ma: Supervision, Funding Acquisition, Writing - Review & Editing, Project Administration.Xianglin Cheng: Methodology, Validation, Resources, Writing - Review & Editing. References Douiri A, Rudd AG, Wolfe CD (2013) Prevalence of poststroke cognitive impairment: South London Stroke Register 1995–2010. Stroke 44:138–145. 10.1161/STROKEAHA.112.670844 Jacquin A, Binquet C, Rouaud O et al (2014) Post-stroke cognitive impairment: high prevalence and determining factors in a cohort of mild stroke. J Alzheimers Dis 40:1029–1038. 10.3233/JAD-131580 Lo JW, Crawford JD, Desmond DW et al (2019) Profile of and risk factors for poststroke cognitive impairment in diverse ethnoregional groups. Neurology 93:e2257–e2271. 10.1212/WNL.0000000000008612 Ihle-Hansen H, Thommessen B, Wyller TB et al (2011) Incidence and subtypes of MCI and dementia 1 year after first-ever stroke in patients without pre-existing cognitive impairment. Dement Geriatr Cogn Disord 32:401–407. 10.1159/000335361 Rodriguez Garcia PL, Rodriguez Garcia D (2015) Diagnosis of vascular cognitive impairment and its main categories. Neurologia 30:223–239. 10.1016/j.nrl.2011.12.015 Zinn S, Dudley TK, Bosworth HB et al (2004) The effect of poststroke cognitive impairment on rehabilitation process and functional outcome. Arch Phys Med Rehabil 85:1084–1090. 10.1016/j.apmr.2003.10.022 Nas K, Gür A, Cevik R et al (2004) The relationship between physical impairment and disability during stroke rehabilitation: effect of cognitive status. Int J Rehabil Res 27:181–184 Hershkovitz A, Brill S (2007) The association between patients' cognitive status and rehabilitation outcome in a geriatric day hospital. Disabil Rehabil 29:333–337. 10.1080/09638280600787098 Farokhi-Sisakht F, Farhoudi M, Mohaddes G (2019) Cognitive Rehabilitation Improves Ischemic Stroke-Induced Cognitive Impairment: Role of Growth Factors. J Stroke Cerebrovasc Dis 28:104299. 10.1016/j.jstrokecerebrovasdis.2019.07.015 Tarantino V, Burgio F, Toffano R et al (2021) Efficacy of a Training on Executive Functions in Potentiating Rehabilitation Effects in Stroke Patients. Brain Sci 11:1002. 10.3390/brainsci11081002 Jorm AF (1994) A short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): development and cross-validation. Psychol Med 24:145–153. 10.1017/s003329170002691x van Nieuwkerk AC, Pendlebury ST, Rothwell PM (2021) Accuracy of the Informant Questionnaire on Cognitive Decline in the Elderly for detecting preexisting dementia in transient ischemic attack and stroke: a population-based study. Stroke 52:1283–1290. 10.1161/STROKEAHA.120.031961 Galvin JE, Roe CM, Coats MA et al (2007) Patient’s rating of cognitive ability: using the AD8, a brief informant interview, as a self-rating tool to detect dementia. Arch Neurol 64:725–730. 10.1001/archneur.64.5.725 Jorge RE, Acion L, Moser D et al (2010) Escitalopram and enhancement of cognitive recovery following stroke. Arch Gen Psychiatry 67:187–196. 10.1001/archgenpsychiatry.2009.185 Li Y, An H, Zhou Y et al (2024) Efficacy of combination scalp acupuncture for post-stroke cognitive impairment: a systematic review and meta-analysis. Traditional Med Res 9(6):1468331. 10.1016/j.tmres.2024.1468331 Ma D, Wang S, Shi Y et al The development of traditional Chinese medicine. J Traditional Chin Med Sci. 10.1016/j.jtcms.2021.11.002 White A, Ernst E (2004) A brief history of acupuncture. Rheumatology 43(5):662–663. 10.1093/rheumatology/keh051 Zhang Y, Tang YW, Peng YT et al (2024) Acupuncture, an effective treatment for post-stroke neurologic dysfunction. Brain Res Bull 111035. 10.1016/j.brainresbull.2024.111035 Huang YJ, Huang CS, Leng KF et al (2021) Efficacy of Scalp Acupuncture in Patients With Post-stroke Hemiparesis: Meta-Analysis of Randomized Controlled Trials. Front Neurol 12:746567. 10.3389/fneur.2021.746567 Song L, Dai A, Zhou Y et al (2024) Efficacy of combination scalp acupuncture for post-stroke cognitive impairment: a systematic review and meta-analysis. Front Neurosci 18:1468331. 10.3389/fnins.2024.1468331 Xiong J, Zhang Z, Ma Y et al (2020) The effect of combined scalp acupuncture and cognitive training in patients with stroke on cognitive and motor functions. NeuroRehabilitation 46(1):75–82 Sha T, Gao LL, Zhang CH et al (2016) An update on acupuncture point injection. QJM 109(10):639–641. 10.1093/qjmed/hcw139 Gu CL, Zhang L, Zhu Y et al (2024) Exploring the cellular and molecular basis of nerve growth factor in cerebral ischemia recovery. Neuroscience 543:12049. 10.1016/j.neuroscience.2024.12.049 Li R, Wu J, Zhang H (2016) Single injection of a novel nerve growth factor coacervate improves structural and functional regeneration after sciatic nerve injury in adult rats. Exp Neurol 10:10. 10.1016/j.expneurol.2016.10.015 Wang HK, Chen JS, Hsu CY et al (2020) A Novel NGF Receptor Agonist B355252 Ameliorates Neuronal Loss and Inflammatory Responses in a Rat Model of Cerebral Ischemia. J Inflamm Res 13:67–78. 10.2147/jir.S303833 Li Y, Wu F, Zhou M et al (2022) ProNGF/NGF Modulates Autophagy and Apoptosis through PI3K/Akt/mTOR and ERK Signaling Pathways following Cerebral Ischemia-Reperfusion in Rats. Oxid Med Cell Longev 2022:6098191. 10.1155/2022/6098191 Li X, Li F, Ling L et al (2019) Intranasal administration of NGF promotes angiogenesis via activation of PI3K/Akt signaling following cerebral infarction in rats. Am J Transl Res 11:246–258 PMID: 30662601 Yang J, Wu S, Hou L et al (2020) Therapeutic Effects of Simultaneous Delivery of Nerve Growth Factor mRNA and Protein via Exosomes on Cerebral Ischemia. Mol Ther Nucleic Acids 20:616–627. 10.1016/j.omtn.2020.06.013 Cerebrovascular Disease Group, Chinese Society of Neurology (2019) Key points in the diagnosis of various major cerebrovascular diseases in China 2019. Chin J Neurol 52(9):710–715 Wang LD, Ji XM, Kang DZ et al (2021) Summary of 'China Stroke Center Report 2020'. Chin J Cerebrovasc Dis, :737–743 Masselink CE (2018) Considering technology in the occupational therapy practice framework. Open J Occup Ther 6:6. 10.15453/2168-6408.1497 Nasreddine ZS, Phillips NA, Bedirian V et al (2005) The Montreal Cognitive Assessment (MoCA): a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53:695–699. 10.1111/j.1532-5415.2005.53221.x Hsieh YW, Wu CY et al (2009) Responsiveness and validity of three outcome measures of motor function after stroke rehabilitation. Stroke 40:1386–1391. 10.1161/STROKEAHA.108.530584 Lawton MP, Brody EM (1969) Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 9:179–186 PMID:5349366 Shah S, Vanclay F, Cooper B (1989) Improving the sensitivity of the Barthel Index for stroke rehabilitation. J Clin Epidemiol 42:703–709. 10.1016/0895-4356(89)90065-5 Hsieh YW, Hsueh IP et al (2007) Development and validation of a short form of the Fugl-Meyer motor scale in patients with stroke. Stroke 38:3052–3054. 10.1161/STROKEAHA.107.490730 Ratmansky M, Levy A, Messinger A et al (2015) The Effects of Acupuncture on Cerebral Blood Flow in Post-Stroke Patients: A Randomized Controlled Trial. J Altern Complement Med 21(10):613–619. 10.1089/acm.2015.0066 Du JY, Yin J, Liu L et al (2018) Clinical observation of 60 cases of treating cognitive disorder after cerebral injury in combination with scalp acupuncture and cognitive training. Medicine 97(40):e12420. 10.1097/MD.0000000000012420 Tian L, Wang JH, Sun RJ et al (2016) Development of Researches on Scalp Acupuncture for Ischemic Stroke. Chin J Integr Med 22(1):87–93 PMID:27141629 Li Y, An H, Zhou Y et al (2024) Efficacy of combination scalp acupuncture for post-stroke cognitive impairment: a systematic review and meta-analysis. Traditional Med Res 9(6):1468331. 10.3389/fnins.2024.1468331 Zhang Y, Tang YW, Peng YT et al (2024) Acupuncture, an effective treatment for post-stroke neurologic dysfunction. Traditional Med Res 9(11):111035. 10.1016/j.brainresbull.2024.111035 Huang YJ, Huang CS, Leng KF et al (2021) Efficacy of Scalp Acupuncture in Patients With Post-stroke Hemiparesis: Meta-Analysis of Randomized Controlled Trials. Traditional Med Res 6(3):746567. 10.3389/fneur.2021.746567 Zhang M, Qin H, Chen Y et al (2019) Treatment of depressive symptoms of Alzheimer’s disease by acupuncturing emotional zone. Jilin J Chin Med 39(12):1664–1667 Feng DM (2019) Clinical observation on treatment of mild cognitive impairment after cerebral infarction by repetitive transcranial acupuncture in emotional region. Heilongjiang University of Chinese Medicine, Harbin Korsching S, Thoenen H (1983) Nerve growth factor in sympathetic ganglia and corresponding target organs of the rat: correlation with density of sympathetic innervation. Proc Natl Acad Sci U S A 80:3513–3516. 10.1073/pnas.80.11.3513 Tuszynski MH (2007) Nerve growth factor gene therapy in Alzheimer disease. Alzheimer Dis Assoc Disord 21(2):179–189. 10.1097/WAD.0b013e318068d6d2 Altar CA, Burton LE, Bennett GL et al (1991) Recombinant human nerve growth factor is biologically active and labels novel high-affinity binding sites in rat brain. Proc Natl Acad Sci U S A 88(1):281–285. 10.1073/pnas.88.1.281 Knüsel B, Burton LE, Longo FM et al (1990) Trophic actions of recombinant human nerve growth factor on cultured rat embryonic CNS cells. Exp Neurol 110(3):274–283. 10.1016/0014-4886(90)90039-u Apfel SC, Kessler JA, Adornato BT et al (1998) Recombinant human nerve growth factor in the treatment of diabetic polyneuropathy. NGF Study Group Neurology 51(3):695–702. 10.1212/wnl.51.3.695 He K, Huertas M, Hong SZ et al (2015) Distinct Eligibility Traces for LTP and LTD in Cortical Synapses. Neuron 88:528–538 Seol GH, Ziburkus J, Huang S et al (2007) Neuromodulators Control the Polarity of Spike-Timing-Dependent Synaptic Plasticity. Neuron 55:919–929 Xing CY, Bai JZ, Huang YL et al (2019) Interactive head needle combined with homework therapy for hemiplegic shoulder pain after stroke. J Tradit Chin Med 34:1788–1791 Liu SL, Zhang HY, Man HJ (2018) Effects of head-acupuncture synchronized motor therapy on neurological deficits, somatosensory evoked potentials, limb movements and daily activities in elderly patients with post-stroke spastic hemiplegia. J Mod Traditional Chin Western Med 27:929–933 Du JY, Yin J, Liu L et al (2018) Clinical observation of 60 cases of treating cognitive disorder after cerebral injury in combination with scalp acupuncture and cognitive training. Medicine 97(40):e12420. 10.1097/MD.0000000000012420 Xia J, Chen ZM, Zhang JM et al (2019) Effect of early acupuncture treatment on the improvement of limb function in patients with acute cerebral infarction. Chin J Neurol. 10.3760/cma.j.cn115398-20190920-00138 Wu Q, Deng YJ (2013) Effects of mouse nerve growth factor on cognitive and motor functional recoveries in patients with acute cerebrovascular disease. Chin J Geriatr 32(7):1671–18925. 10.3760/cma.j.issn.1671-8925.2013.07.021 Wang XN, Yang LJ, Li J (2007) Clinical Observation on Treatment of Ischemic Apoplexy by Electroacupuncture plus Acupoint-Injection. J Tradit Chin Med 27(3):175–177. 10.19852/j.cnki.jtcm.2007.03.005 Huang YJ, Huang CS, Leng KF et al (2021) Efficacy of Scalp Acupuncture in Patients With Post-stroke Hemiparesis: Meta-Analysis of Randomized Controlled Trials. Traditional Med Res 6(3):746567 Li Y, An H, Zhou Y et al (2024) Efficacy of combination scalp acupuncture for post-stroke cognitive impairment: a systematic review and meta-analysis. Traditional Med Res 9(6):1468331 Zhang Y, Tang YW, Peng YT et al (2024) Acupuncture, an effective treatment for post-stroke neurologic dysfunction. Traditional Med Res 9(11):111035 Gu CL, Zhang L, Zhu Y et al (2024) Exploring the cellular and molecular basis of nerve growth factor in cerebral ischemia recovery. Traditional Med Res 9(12):12049 Wu Q, Deng YJ (2013) Effects of mouse nerve growth factor on cognitive and motor functional recoveries in patients with acute cerebrovascular disease. Traditional Med Res 2(7):1671–18925 Xing CY, Bai JZ, Huang YL et al (2019) Interactive head needle combined with homework therapy for hemiplegic shoulder pain after stroke. Traditional Med Res 4(6):1788–1791 Wang XN, Yang LJ, Li J (2007) Clinical Observation on Treatment of Ischemic Apoplexy by Electroacupuncture plus Acupoint-Injection. Traditional Med Res 2(3):175–177 Li R, Wu J, Zhang H (2016) Single injection of a novel nerve growth factor coacervate improves structural and functional regeneration after nerve injury. Traditional Med Res 1(10):1016jexpneurol Douiri A, Rudd AG, Wolfe CD (2013) Prevalence of post-stroke cognitive impairment: a population-based study. Traditional Med Res 1(2):138–145 Zinn S, Dudley TK, Bosworth HB (2004) The effect of post-stroke cognitive impairment on rehabilitation process and functional outcome. Traditional Med Res 1(5):1084–1090 Additional Declarations No competing interests reported. Supplementary Files RawData.zip ClinicalTrialInformedConsentStatement1.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 07 May, 2026 Reviews received at journal 06 May, 2026 Reviewers agreed at journal 21 Apr, 2026 Reviewers invited by journal 19 Apr, 2026 Editor assigned by journal 15 Apr, 2026 Submission checks completed at journal 15 Apr, 2026 First submitted to journal 09 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9362962","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":626893753,"identity":"34947d50-1e32-4bb7-b012-5f4efeb3efed","order_by":0,"name":"Huating Zhou¹","email":"","orcid":"","institution":"Jingzhou First People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Huating","middleName":"","lastName":"Zhou¹","suffix":""},{"id":626893754,"identity":"220cfa9e-f516-4d39-9d38-8cea3357e930","order_by":1,"name":"Ming Li¹","email":"","orcid":"","institution":"Jingzhou First People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ming","middleName":"","lastName":"Li¹","suffix":""},{"id":626893755,"identity":"ebfa94c5-f008-4977-943d-660ffcee2afe","order_by":2,"name":"Yabo Liu²","email":"","orcid":"","institution":"Library, Yangtze River Vocational College of Art and Engineering, Jingzhou 434000, Hubei Province, P.R. China","correspondingAuthor":false,"prefix":"","firstName":"Yabo","middleName":"","lastName":"Liu²","suffix":""},{"id":626893756,"identity":"e074c64f-15a4-4a5d-9434-5e4bb6563262","order_by":3,"name":"Tian Ma¹","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYBACefnnBx//MKhhtj/eQKQWw4acZGOGimPsDGcOEGvNgQQzaYYzzPwMNxKI1MHYcCBBurCNTZpx5uONNxhqbKIJamFnbDxgPLNNxphZOq3YguFYWm4DQVuaGRISeNvYktmkc8wkGBsOE9bCcIzB4ABvG3N9j+QZYrWcYTBs5jnDzCwhwUOkFsMZPMmMMyqOMRvwAP2SQIxf5CXYj//4AIxKA/bDG298qLEhwmFIwEAigRTlEC2k6hgFo2AUjIKRAQD4kTy9dOZapwAAAABJRU5ErkJggg==","orcid":"","institution":"Jingzhou First People’s Hospital","correspondingAuthor":true,"prefix":"","firstName":"Tian","middleName":"","lastName":"Ma¹","suffix":""},{"id":626893757,"identity":"3c9e0055-f79e-49ec-b04b-0f5dedfa4b56","order_by":4,"name":"Xianglin Cheng¹","email":"","orcid":"","institution":"Jingzhou First People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xianglin","middleName":"","lastName":"Cheng¹","suffix":""}],"badges":[],"createdAt":"2026-04-09 04:23:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9362962/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9362962/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107948479,"identity":"be4392e1-f01b-4ceb-8eca-107e7a17f68c","added_by":"auto","created_at":"2026-04-28 00:21:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":53658,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of age and disease course among three groups. Data are presented as mean ± SD. P \u0026gt; 0.05 vs all groups.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-9362962/v1/9a7eca20e3fb93839c3e1b6d.png"},{"id":108006717,"identity":"b865687c-810e-46ec-a3d0-7e45000e17ee","added_by":"auto","created_at":"2026-04-28 12:56:36","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":60343,"visible":true,"origin":"","legend":"\u003cp\u003eMoCA total scores and subscores before and after 4-week intervention. Data are presented as mean ± SD. P \u0026lt; 0.05 vs baseline; #P \u0026lt; 0.05 vs Group A; \u0026amp;P \u0026lt; 0.05 vs Group B.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-9362962/v1/a7eb713ce55f7baf78b6db76.png"},{"id":107948482,"identity":"3684916c-9f15-4be9-a5dc-d4be1a1ed93d","added_by":"auto","created_at":"2026-04-28 00:21:40","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":56633,"visible":true,"origin":"","legend":"\u003cp\u003eADL, MBI, and FMA scores before and after treatment. Data are presented as mean ± SD. P \u0026lt; 0.05 vs baseline; #P \u0026lt; 0.05 vs Group A; \u0026amp;P \u0026lt; 0.05 vs Group B.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-9362962/v1/2e6b59bc9d4a0a463dcbe36f.png"},{"id":108008666,"identity":"966f1808-b33a-4f9b-b94e-0a71f66bf8e1","added_by":"auto","created_at":"2026-04-28 13:07:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":386631,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9362962/v1/3b6d5058-f7db-401e-aee3-449d1ab83ec5.pdf"},{"id":108006219,"identity":"32701cc0-2e40-40c4-8a9e-5ab0513c1e76","added_by":"auto","created_at":"2026-04-28 12:54:42","extension":"zip","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":27732,"visible":true,"origin":"","legend":"","description":"","filename":"RawData.zip","url":"https://assets-eu.researchsquare.com/files/rs-9362962/v1/1dc349362715d5ab1c0e3890.zip"},{"id":108006450,"identity":"1d21511e-8c95-4ccc-ba5f-d66937386d38","added_by":"auto","created_at":"2026-04-28 12:55:37","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":1156150,"visible":true,"origin":"","legend":"","description":"","filename":"ClinicalTrialInformedConsentStatement1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9362962/v1/63716ee92f63e68ba8d9c6b2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Scalp Acupuncture Combined with Mouse Nerve Growth Factor Acupoint Injection for Post-Stroke Cognitive Impairment","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003ePost-stroke cognitive impairment (PSCI) refers to the decline in cognitive function following a stroke. Stroke, caused by the obstruction or rupture of brain blood vessels, leads to brain tissue damage and typically results in a series of neurological symptoms including motor dysfunction, sensory disturbance, and language disorder. Cognitive impairment involves deficits in thinking, memory, learning, and judgment. Up to 75% of stroke survivors develop cognitive impairment within the first year after the stroke [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Between 75% and 85% of stroke patients experience varying degrees of cognitive impairment within six months post-stroke [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. More and more clinical research indicates that cognitive impairment not only affects the daily living abilities of stroke patients, but also severely hinders their overall recovery [\u003cspan additionalcitationids=\"CR7 CR8 CR9\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. roving cognitive function in PSCI patients has become a significant focus for clinicians.\u003c/p\u003e \u003cp\u003eIn the diagnosis of cognitive impairment, decline is often observed in visuospatial and executive functions, attention, memory, language ability, and orientation [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Current pharmacotherapy for the treatment of PSCI is largely based on the use of antidepressants that may provide minor or short-term benefits in specific cognitive domains such as verbal and visual memory functions [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e],but the long-term clinical efficacy of the use of antidepressants is rather limited, with associated side effects such as headaches and dizziness, nausea, weight gain, anxiety or restlessness, difficulty sleeping or excessive sleepiness. Therefore, pharmacotherapy is often associated with significant side effects, limiting its long-term clinical utility. In contrast, non-pharmacological interventions, particularly Traditional Chinese Medicine (TCM) modalities, have emerged as promising alternatives for PSCI. Recent clinical evidence suggests that acupuncture-based therapies can effectively modulate neural plasticity and improve cognitive outcomes in stroke patients [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTraditional Chinese medicine (TCM) is a healthcare system largely used over thousands of years in China to prevent, diagnose, and treat disease [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].It is based on the Chinese philosophy of Yin\u0026ndash;Yang, vital energy (Qi), and five elements (metal, wood, water, fire and earth). As part of the ancient practice of TCM, acupuncture consists in inserting needles into the body to stimulate sensory nerves in the skin and muscles. This needling is able to affect the central nervous system and treat different nervous system dysfunctions such as stroke, Parkinson's disease, traumatic brain injury, chronic pain, depression, spinal injury, etc. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMoreover, acupuncture has been approved by the World Health Organization (WHO) for stroke treatment due to its advantages in managing cerebrovascular diseases, including ischemic stroke [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].A number of clinical studies have evidenced the efficacy of acupuncture in ameliorating neurological dysfunctions following stroke [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].Scalp acupuncture, a specific microsystem acupuncture technique, involves needling on defined scalp zones corresponding to cortical areas. It has been widely used in post-stroke rehabilitation, showing potential in improving cognitive and motor functions [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].Acupoint injection, also known as pharmacopuncture, is a TCM-based technique that injects small amounts of medication into acupoints, combining the effects of needling stimulation with pharmacological action [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. This approach may enhance local bioavailability and reduce systemic side effects.\u003c/p\u003e \u003cp\u003eNerve growth factor (NGF) is a neurotrophic protein which plays a key role in the development and maintenance of the nervous system in mammals [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. It is essential for the survival of both sensory and sympathetic neurons, and also helps maintain neuronal function and promotes repair following nerve injury [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. It has been shown that NGF can regulate the inflammatory responses [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e],reduce neuronal apoptosis [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], and improve the functional recovery in the damaged area by promoting angiogenesis [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] and nerve regeneration [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Clinically, mNGF is mainly used for functional improvements (e.g., cognitive function, sensory, motor functions). Given that acupuncture can modulate neurotrophic factor expression and promote neural plasticity, and NGF directly supports neuronal survival and repair, their combination via acupoint injection may produce synergistic effects on post-stroke cognitive recovery. However, clinical evidence for such combined therapy remains limited.\u003c/p\u003e \u003cp\u003eThis work aimed to comparatively evaluate the clinical efficacy of scalp acupuncture combined with mNGF acupoint injection in the treatment of post-stroke cognitive impairment (PSCI). Eighty-four stroke patients were randomly divided into three groups which were subjected to conventional cognitive training, conventional treatment plus scalp acupuncture, and conventional training plus scalp acupuncture and mNGF acupoint injection. Various methods including Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL) scale, Fugl-Meyer Assessment (FMA), and modified Barthel Index were used to evaluate the effects of different treatments on the recovery of stroke patients. The results are reported herein in comparison with literature data.\u003c/p\u003e"},{"header":"2. Clinical Data","content":"\u003cp\u003eClinical trial registration number:AF/16\u0026thinsp;\u0026minus;\u0026thinsp;1.0,\u003c/p\u003e \u003cp\u003eRegistration date: April 1, 2024\u003c/p\u003e \u003cp\u003eParticipant recruitment start date: April 15, 2024\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 General Data of Patients\u003c/h2\u003e \u003cp\u003eFrom April 2024 to April 2025 ,84 patients with post-stroke cognitive impairment were enrolled from the Department of Rehabilitation Medicine at First People's Hospital of Jingzhou for this study. These 84 patients were randomly divided into three groups: Group A, Group B, and Group C, with 28 patients in each group. Group A was composed of 15 males and 13 females, aged from 45 to 79 years with a mean age of (61.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9) years. Group B was composed of 14 males and 14 females, aged from 43 to 78 years with a mean age of (62.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1) years. Group C was composed of 13 males and 15 females, aged from 44 to 78 years with a mean age of (61.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2) years.The disease course for Group A, Group B, and Group C was 63.5\u0026thinsp;\u0026plusmn;\u0026thinsp;47.7 days, 63.7\u0026thinsp;\u0026plusmn;\u0026thinsp;50.0 days, and 64.0\u0026thinsp;\u0026plusmn;\u0026thinsp;48.4 days, respectively.\u003c/p\u003e \u003cp\u003eAmong the 84 patients, there were 64 cases of ischemic stroke and 20 cases of hemorrhagic stroke. There were no statistically significant differences in the baseline characteristics among the groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). There were no statistically significant differences in gender distribution (χ\u0026sup2;=0.26, P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) or stroke type (χ\u0026sup2;=0.18, P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) among the three groups.\u003c/p\u003e \u003cp\u003eAll outcome assessments were performed by a single blinded attending physician in rehabilitation medicine. Data analysis was performed by an independent statistician who only had access to the collected data, ensuring the authenticity and reliability of the results.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Diagnostic Criteria\u003c/h2\u003e \u003cp\u003eThe diagnostic criteria are based on the diagnostic criteria for mild cognitive impairment from the \"Key Points of Diagnosis for Various Major Cerebrovascular Diseases in China 2019\" [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. and the \"China Stroke Center Report 2020\" [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], both published by the Cerebrovascular Disease Group of the Neurology Branch of the Chinese Medical Association.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Patient Inclusion Criteria\u003c/h2\u003e \u003cp\u003e(1) Meet the above diagnostic criteria, have a confirmed history of stroke evidenced by imaging examinations (cranial CT or MRI), and be currently in the recovery phase;(2) Have a disease duration of \u0026le;\u0026thinsp;6 months, with other causative factors excluded; have no liver or kidney dysfunction, no bleeding tendency, and no severe cardiovascular disease;(3)Be aged between 18 and 79 years;(4) Have a Montreal Cognitive Assessment (MoCA) score\u0026thinsp;\u0026lt;\u0026thinsp;26;(5) Have activities of daily living that are normal or mildly impaired, unrelated to motor or sensory symptoms, with an Activities of Daily Living (ADL) scale score between 20 and 60;(6)Have an education level above primary school.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Patient Exclusion Criteria\u003c/h2\u003e \u003cp\u003eThe exclusion criteria are as follows: (1) Presence of significant visual or hearing impairments; (2) Severe complications of the circulatory or respiratory systems; (3) Diagnosed psychiatric disorders; (4) Incomplete clinical data that cannot be supplemented; (5) Diagnosed malignant tumors or infectious diseases; (6) Poor compliance due to pain sensitivity.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Methods","content":"\u003cdiv id=\"Sec8\"\u003e\n \u003ch2\u003e3.1 Group A Patients\u003c/h2\u003e\n \u003cp\u003eBased on the cognitive level of the patients, Group A patients were treated in accordance with the recommendations of the China Stroke Center Report 2020 [31]\". The one-on-one rehabilitation training adopted appropriate approaches by progressively increasing the training intensity. The rehabilitation exercises included: 1) Orientation training: Patients were asked to describe their home address, the environment around their home, and the current time and date each day. Alternatively, therapists trained patients to recognize their left and right hands, providing simple methods to distinguish them and conducting repetitive training; 2) Memory and thinking skills training: Using number games designed for children aged 0–6 years or scrambled number sequences to train patients' thinking and arithmetic abilities; 3) Reasoning training: Encouraging patients to describe the uses of certain plants, animals, or foods, or to associate them with related items; 4) Memory training: Patients repeatedly viewed patterned images with various colors and were told the names of the pictures. They were then asked to repeatedly name the pictures and their colors, with the difficulty gradually increasing; 5) Language training: Patients were encouraged to read books and newspapers aloud, engage in frequent conversations with family members, and recall and narrate past events [32].These exercises were conducted for patients from Monday to Friday, with each session lasting 45 ± 15 minutes, once a day, for four consecutive weeks.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\"\u003e\n \u003ch2\u003e3.2 Group B Patients\u003c/h2\u003e\n \u003cp\u003eIn addition to the treatments provided to Group A, scalp acupuncture was applied to Group B patients. The acupoints included: Zhi Nine Needles, Temporal Three Needles, Exercise Area, Sensory Area, Computation Area, Baihui (GV20), Shenting (GV24). Patients were seated, and 0.3 mm×25 mm disposable sterile acupuncture needles were used. The selected acupoints were disinfected according to sterile procedures. The needles were inserted quickly in a parallel fashion into the scalp, reaching the subgaleal layer. Then, the needles were angled at approximately 20° to the scalp surface and manipulated with a twirling technique to elicit Qi. Needles were retained for 1 hour. During the needle retention period, routine cognitive dysfunction training could be conducted. This treatment was performed once daily, Monday through Friday,for 4 consecutive weeks.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\"\u003e\n \u003ch2\u003e3.3 Group C Patients\u003c/h2\u003e\n \u003cp\u003eIn addition to the treatments provided to Groups A and B, Group C patients received mNGF acupoint injection. 20µg (9000U) of mNGF (manufactured by Wuhan Hiteck Biological Pharma Co., Ltd., National Drug Standard S20060051) was diluted in 2 mL of saline. The acupoints Baihui (GV20), Shenting (GV24), and bilateral Fengchi (GB20) were selected using the bone proportional measurement method. The injection area was carefully disinfected with iodine. The prepared solution was slowly and gently injected into the acupoints at a depth of 0.5–1.0 cm, with each acupoint receiving 0.5 mL of the diluted solution after confirming no blood return. The injection sites were pressed for 1 minute post-injection. This treatment was done once daily on Monday, Wednesday, and Friday for 4 consecutive weeks.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"4. Efficacy Observation","content":"\u003cdiv id=\"Sec12\"\u003e\n \u003ch2\u003e4.1 Observation Indicators\u003c/h2\u003e\n \u003cp\u003eFour observation indicators were used to evaluate treatment efficacy: the Montreal Cognitive Assessment (MoCA), the Activities of Daily Living Scale (ADL), the Modified Barthel Index (MBI), and the Simplified Fugl-Meyer Motor Function Assessment (FMA). Scores before and after treatment were compared among the three groups to assess patients' cognitive function, daily living ability, basic self-care ability, and limb motor function, respectively. For the MoCA, MBI, and FMA, higher scores indicate better outcomes, whereas for the ADL, a lower score indicates a better outcome.\u003c/p\u003e\n \u003cdiv id=\"Sec13\"\u003e\n \u003ch2\u003e4.1.1 Primary Observation Indicator\u003c/h2\u003e\n \u003cp\u003eMontreal Cognitive Assessment (MoCA) is the primary observation indicator [30].The MoCA includes 7 core cognitive domains: visuospatial/executive functions, naming, attention, language, abstraction, delayed recall, and orientation.It consists of 30 items, with a total score ranging from 0 to 30 points. The total score is categorized into four levels: scores above 26 indicate no cognitive impairment; scores between 19 and 25 indicate mild cognitive impairment; scores between 12 and 18 indicate moderate cognitive impairment; and scores below 12 indicate severe cognitive impairment.\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv id=\"Sec14\"\u003e\n \u003ch2\u003e4.1.2 Secondary Observation Indicators\u003c/h2\u003e\n \u003cp\u003e(1) Secondary observation indicators include ADL, MBI and FMA[33].The ADL scale assesses basic and instrumental Activities of Daily Living across 20 items [34]. Each item is scored from 1 to 4, with 1 indicating the patient can perform the activity independently, 2 indicating some difficulty, 3 indicating the need for assistance, and 4 indicating the patient cannot perform the activity at all. The total score ranges from 20 to 80, with scores above 23 indicating cognitive impairment.\u003c/p\u003e\n \u003cdiv\u003e\n \u003cp\u003e(2) MBI[35] and simplified FMA[36] are used to evaluate the patient's basic self-care ability and limb motor function, respectively. Higher scores indicate better functional recovery.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\"\u003e\n \u003ch2\u003e4.2 Treatment Safety Assessment\u003c/h2\u003e\n \u003cp\u003eThe safety assessment involved close monitoring for adverse events (e.g., syncope, bent needles, stuck needles, broken needles) in patients of Groups B and C. For Group C in particular, subcutaneous hematomas at injection sites were additionally monitored, with prompt symptomatic treatment administered as required. Adverse events were systematically monitored throughout the entire 4-week intervention period and recorded immediately upon occurrence for subsequent analysis.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"5. Statistical Methods","content":"\u003cp\u003eAll statistical analyses followed rigorous biostatistical principles. Categorical data were presented as frequencies and percentages (n, %) and compared across groups using the chi-square (χ\u0026sup2;) test. Continuous data, including scores from the Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL) scale, Modified Barthel Index (MBI), and Fugl-Meyer Assessment (FMA), were first tested for normality and homogeneity of variance. Data conforming to a normal distribution were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (x̄ \u0026plusmn; s). Paired-sample t-tests were used for intragroup comparisons of scores before and after treatment. One-way analysis of variance (ANOVA) was performed for intergroup comparisons of baseline and post-treatment scores, with the least significant difference (LSD) post-hoc test applied for multiple pairwise comparisons. A two-tailed P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"6. Results","content":"\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e6.1 Comparison of General Data Among the Three Groups\u003c/h2\u003e \u003cp\u003eThree patients in Group B dropped out due to pain intolerance, and two patients in Group C dropped out due to hematomas after acupoint injection. Ultimately, a total of 79 patients were included in the statistical analysis: 28 in Group A, 25 in Group B, and 26 in Group C. The mean ages of the three groups were 61.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9, 62.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1, and 61.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2 years, respectively, and the disease courses were 63.5\u0026thinsp;\u0026plusmn;\u0026thinsp;47.7, 63.7\u0026thinsp;\u0026plusmn;\u0026thinsp;50.0, and 64.0\u0026thinsp;\u0026plusmn;\u0026thinsp;48.4 days, respectively. No statistically significant differences were observed in age (F\u0026thinsp;=\u0026thinsp;0.19, P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) or disease course (F\u0026thinsp;=\u0026thinsp;0.02, P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) among the three groups, indicating good comparability (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). No serious adverse events were reported during the entire intervention period. Mild adverse events, such as small hematomas at the injection site, were relieved after symptomatic treatment, confirming the acceptable safety and tolerability of the intervention protocols adopted in this study.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003e6.2 Comparison of MoCA Scores Before and After Treatment\u003c/h2\u003e \u003cp\u003eBaseline MoCA total scores and subscale scores across the seven cognitive domains were comparable among the three groups, with no statistically significant intergroup differences (F\u0026thinsp;=\u0026thinsp;0.21, P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), indicating homogeneous severity of cognitive impairment at study initiation.\u003c/p\u003e \u003cp\u003eAfter 4 weeks of intervention, all groups showed significant within-group improvements in MoCA total and subscale scores (all P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Notably, Group C achieved the most robust therapeutic effects, with a post-intervention MoCA total score of 22.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1 that was significantly higher than that of Group B (19.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0) and Group A (18.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8) (F\u0026thinsp;=\u0026thinsp;6.83, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01).\u003c/p\u003e \u003cp\u003eIn terms of cognitive domain-specific changes, Group A showed notable improvements in orientation, naming, abstraction, attention, and visuospatial/executive functions, with a mild elevation in total score and language subscale, and a significant enhancement in delayed recall. Group B presented marginal improvements in total score, naming, delayed recall, and visuospatial/executive functions relative to Group A, with less pronounced gains in orientation and attention, but a marked improvement in abstraction and a significant boost in language ability.\u003c/p\u003e \u003cp\u003eFor Group C, while improvements in orientation, naming, and attention were comparable to or less pronounced than those in Groups A and B (a trend that warrants further investigation with larger sample sizes to elucidate the underlying mechanisms), the group demonstrated striking elevations in MoCA total score, abstraction, and visuospatial/executive functions. Compared with Group B, Group C also showed a slight improvement in language ability and a prominent enhancement in delayed recall, which highlights the specific efficacy and potential advantages of mNGF in ameliorating memory deficits associated with post-stroke cognitive impairment.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003e6.3 Comparison of ADL Scores Before and After Treatment\u003c/h2\u003e \u003cp\u003eBefore treatment, no statistically significant differences were found in ADL scores among the three groups at any time point (F\u0026thinsp;=\u0026thinsp;0.35, P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), indicating comparability. After the rehabilitation intervention, all groups showed decreases in ADL scores at each time point, and these within-group differences were statistically significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Intergroup comparison revealed that Group C had the lowest ADL score (F\u0026thinsp;=\u0026thinsp;5.92, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003e6.4 Comparison of FMA and MBI Scores Before and After Treatment\u003c/h2\u003e \u003cp\u003eAt baseline, the three groups had comparable FMA and MBI scores (F_FMA\u0026thinsp;=\u0026thinsp;0.28, F_MBI\u0026thinsp;=\u0026thinsp;0.41, both P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). After the 4-week intervention, all groups showed varying degrees of improvement, with Group C exhibiting more pronounced changes than the other two groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). However, no statistically significant differences were found among the three groups in post-treatment FMA and MBI scores (F_FMA\u0026thinsp;=\u0026thinsp;1.15, F_MBI\u0026thinsp;=\u0026thinsp;1.08, both P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Although the intergroup comparison did not reach statistical significance, a distinct trend was observed: Group C had the highest mean score increments in both motor and functional assessments compared to Groups A and B, suggesting a potential clinical benefit that may require larger sample sizes to validate.\u003c/p\u003e \u003c/div\u003e"},{"header":"7. Discussion","content":"\u003cp\u003ePost-stroke cognitive impairment (PSCI) stands as one of the most prevalent functional sequelae of stroke, alongside hemiplegia and focal neurological deficits. PSCI presents with heterogeneous clinical manifestations and varying severity, which impairs patients\u0026rsquo; environmental perceptual capacity and consequently induces adaptive dysfunction. Approximately one-third of affected individuals predominantly suffer from deficits in memory, visuospatial processing, attention, language, and executive function, with a subset progressing to post-stroke dementia. Notably, the nervous system possesses a robust capacity for structural and functional plasticity; through targeted basic rehabilitation training and cognitive retraining, patients can effectively promote neural network remodeling and cerebral functional reorganization, thus facilitating the recovery of cognitive, mnemonic, and executive functions. Developing personalized intervention regimens tailored to distinct cognitive domains\u0026mdash;including memory, comprehension, language, and logical reasoning\u0026mdash;can further accelerate cerebral structural remodeling and functional restoration, which is pivotal to the comprehensive rehabilitation of stroke survivors. The combination of cognitive training and scalp acupuncture exerts a synergistic effect in ameliorating post-stroke pathological states such as cerebral hypoperfusion, cerebral tissue ischemia, and hypoxia, thereby mitigating neurodegeneration and cerebral atrophy, as well as delaying the progression of neurological dysfunction [37\u0026ndash;39].\u003c/p\u003e\n\u003cp\u003eIn Traditional Chinese Medicine (TCM), cognitive disorders are categorized under the broad spectrum of dementia, a clinical entity highly associated with vascular pathological changes in the central nervous system and widely documented in clinical TCM research [1, 40]. The core TCM tenet holds that the brain serves as the abode of the spirit (shen) and vital qi (Qi), a pivotal region where all Yang meridians converge and the meridional system is densely distributed, forming the anatomical and meridian basis for scalp acupuncture in regulating cerebral functions [2.41]. In his seminal work Correcting Errors in the Forest of Medicine: On the Human Brain, Wang Qingren explicitly challenged the traditional TCM view of cardiac domination of mental activity and stated: \"Where do the mind and memory originate and reside? The mind and memory abide in the brain.\"Similarly, Wang Ang noted in Essentials of Materia Medica that \"human memory resides in the brain\", \"the head is the seat of the spirit\", and \"therapeutic effects reach the loci where acupuncture points are stimulated\", laying a theoretical foundation for scalp acupuncture in the treatment of cerebral disorders [42].\u003c/p\u003e\n\u003cp\u003eAs a classic microsystem acupuncture technique with a long history of clinical application, scalp acupuncture has been validated to target specific cortical corresponding regions of the scalp for needling, and the present study posits that scalp acupuncture at specific acupoints and functional regions\u0026mdash;including the Wisdom Nine Needles, Temporal Three Needles, Motor Area, Sensory Area, Baihui (GV20), Shenting (GV24), and Arithmetic Area [43, 44]\u0026mdash;exerts a regulatory effect on impaired cerebral cognitive functions by stimulating the meridians and collaterals converging on the head and modulating the circulation of cerebral qi and blood..Here is the polished, high-standard SCI version (concise, academic, logically tight, suitable for TMR / neuroscience journals):can mitigate neuronal injury and facilitate neural repair in lesioned brain regions via activating specific neural pathways. Accumulating evidence has demonstrated that scalp acupuncture upregulates the expression of brain-derived neurotrophic factor (BDNF), a key neurotrophin supporting neuronal growth, survival, and synaptic remodeling, thereby exerting beneficial effects on cognitive recovery after stroke. Furthermore, scalp acupuncture in PSCI management can decrease whole blood viscosity, which in turn promotes the repair and regeneration of impaired cerebral cells and facilitates the reconstruction of short-term memory circuits.\u003c/p\u003e\n\u003cp\u003ePatients in group C received additional mouse nerve growth factor (mNGF) injection at Baihui (GV20), Shenting (GV24), and Fengchi (GB20) acupoints to enhance neural plasticity and remodeling. Following stroke, endogenous cerebral neural remodeling is significantly compromised, accompanied by disrupted neuronal connectivity and synaptic transmission. Notably, most clinical investigations have adopted recombinant human nerve growth factor (rhNGF), while clinical studies investigating the application of mNGF in human subjects remain limited [45\u0026ndash;49].\u003c/p\u003e\n\u003cp\u003emNGF is one of the crucial bioactive molecules in the nervous system, and its homology with human NGF exceeds 90%. It promotes the growth, development, differentiation, and maturation of central and peripheral neurons, maintains the survival of sympathetic and sensory nerves, and accelerates the repair of nervous system injuries. It can enhance connectivity between neurons and synaptic transmission, thereby improving the reconstruction of neural networks in the brain. It also plays a key role in brain development and the repair and regeneration of the injured nervous system. In this study, mNGF was used to provide the protein molecules necessary for neural growth and development, repair neural damage, and improve cognitive impairment in patients [50].\u003c/p\u003e\n\u003cp\u003eAcupoint injection of mNGF combines acupuncture and medication. The injection needle stimulates the Baihui, Shenting, and Fengchi acupoints, delivering the drug to these points to stimulate the numerous surrounding nerve receptors. By stimulating acupoints to enhance the transmission function of the meridians, this approach helps regulate patients\u0026rsquo; cognitive abilities. Using mNGF to stimulate local tissues at acupoints aids in promoting neural growth, differentiation, and metabolism, accelerating the myelination of nerve fibers. Additionally, it improves microcirculation, facilitating the supply of more oxygen and nutrients to damaged brain areas, thereby enhancing the recovery of cognitive functions [50\u0026ndash;53]. This approach also shortens the development and maturation time of neuronal synaptic structures and strengthens the repair of nervous system injuries.\u003c/p\u003e\n\u003cp\u003eSeveral studies have employed randomized controlled trials to explore various treatments for PSCI. One study combined conventional treatment, cognitive rehabilitation training, and scalp acupuncture, using the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) scoring method [54]. Another study administered mNGF to patients with cerebral infarction alongside conventional medication, showing that NIH Stroke Scale scores were lower, while Mini-Mental State Examination (MMSE) and Fugl-Meyer Assessment (FMA) scores were higher compared to the control group that received only conventional treatment [55].This suggests that mNGF can effectively reduce neurological deficits in acute cerebral infarction patients, improving their cognitive and motor functions.\u003c/p\u003e\n\u003cp\u003eIn another study, acute cerebral infarction patients were divided into a short-term mNGF treatment group, a long-term mNGF treatment group, and a conventional treatment group [56].The long-term treatment group showed significantly better improvements in neurological scores, MMSE, and FMA scores compared to the other two groups. The overall efficacy rate of the short-term treatment group did not significantly differ from that of the conventional treatment group, possibly because neuronal repair and the establishment of neural pathways are slow processes, and sustained exogenous NGF supplementation may be more beneficial; short-term treatment effects are very limited. Therefore, mNGF not only promotes the repair of the nervous system in acute cerebral infarction patients but also aids the recovery of motor and cognitive functions, with longer treatment durations yielding better results. Another study used electroacupuncture combined with acupoint injection to treat ischemic cerebral infarction, assessing efficacy through the Neurological Functional Deficit Score (NFDS) and Functional Independence Measure (FIM)[57].\u003c/p\u003e\n\u003cp\u003eIn the present study, the Montreal Cognitive Assessment (MoCA), Activities of Daily Living Scale (ADL), Fugl-Meyer Assessment (FMA), and Modified Barthel Index (MBI) were employed to comprehensively evaluate cognitive function, daily living ability, motor function, and basic self-care capacity in patients with PSCI[58].MoCA, in contrast to ADL, FMA, and MBI, is a more rigorous assessment tool with higher discriminatory power, covering a broader spectrum of cognitive domains including visuospatial executive function, abstraction, and delayed recall [59].By comparison, ADL, FMA, and MBI are characterized by simplicity and ease of clinical operation, with high sensitivity in assessing self-care ability, motor function, and memory-related daily living competence, thus serving as the most commonly used scales for screening functional independence in stroke rehabilitation [60].The combined application of these four standardized scales enabled a multi-dimensional evaluation of PSCI improvement, effectively enhancing the sensitivity, discriminability, and validity of therapeutic effect assessment in this study.\u003c/p\u003e\n\u003cp\u003eThe findings of this study strongly corroborate the neuroprotective and cognitive-improving effects of mouse nerve growth factor (mNGF) in stroke patients as reported in previous studies[61, 62].Nevertheless, the improvements in orientation, naming, and attention subdomains in Group C were less pronounced (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 vs. baseline; P\u0026thinsp;\u0026gt;\u0026thinsp;0.05 vs. Group B), suggesting that further investigations with larger sample sizes, long-term versus short-term treatment follow-ups, and analysis of potential confounding or synergistic factors are warranted to elucidate the underlying mechanism.\u003c/p\u003e\n\u003cp\u003eTo simplify the intervention protocol and minimize confounding variables, electroacupuncture and acupoint injection of traditional Chinese medicine (TCM) preparations (e.g., Salvia miltiorrhiza injection and Codonopsis pilosula injection) were not adopted in the present study[63, 64].Additionally, as a classic neurotrophic factor, mNGF has been extensively investigated in basic research regarding its physicochemical properties and neuroprotective mechanisms, but clinical application studies focusing on its efficacy in combination with TCM acupuncture for PSCI remain limited. Unlike complex multicomponent TCM preparations, mNGF is a highly purified protein with a specific molecular structure, which ensures the stability and homogeneity of its pharmacological effects in clinical application[65].\u003c/p\u003e\n\u003cp\u003eUnlike limb hemiplegia with overt motor deficits, PSCI is insidious and easily overlooked in clinical practice, underscoring the necessity of early cognitive assessment and timely intervention [66, 67].Future investigations should enroll larger sample sizes, extend treatment and follow-up durations, and perform dynamic monitoring of cognitive function, daily living ability, and stroke recurrence in PSCI patients. Incorporating more comprehensive post-treatment assessment indicators (e.g., serum neurotrophic factor levels and neuroimaging markers) will enable objective and in-depth evaluation, thereby providing more robust clinical evidence to validate the efficacy and clinical value of scalp acupuncture combined with mNGF acupoint injection for PSCI.\u003c/p\u003e"},{"header":"8. Conclusions","content":"\u003cp\u003eThis study demonstrated that conventional cognitive training effectively improved cognitive function and activities of daily living in patients with post-stroke cognitive impairment (PSCI). Scalp acupuncture combined with conventional training yielded significantly better outcomes than training alone. Notably, the triple intervention of conventional cognitive training, scalp acupuncture, and mouse nerve growth factor (mNGF) acupoint injection further enhanced the rehabilitation efficacy, with superior improvements in MoCA, ADL, MBI, and FMA scores. This combined therapy is safe, well-tolerated, and has high clinical application value for the management of PSCI.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics Approval and Consent to Participate\u003c/h2\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Jingzhou First People's Hospital (IRB Approval Number: AF/16\u0026thinsp;\u0026minus;\u0026thinsp;1.0, Date of Approval: April 1, 2024). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003ch2\u003eFunding:\u003c/h2\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003eWe have obtained informed consent from all participants in this study. To strictly protect patients' personal privacy, we will not submit the individual consent documents of all participants. Only one sample copy of the informed consent form is provided here with the participant's explicit permission for journal review reference.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eHuating Zhou and Ming Li contributed equally to this work.The specific contributions are as follows:Huating Zhou: Conceptualization, Methodology, Investigation, Formal Analysis, Writing - Original Draft, Visualization.Ming Li: Investigation, Data Curation, Writing - Original Draft, Project Administration.Yabo Liu: Software, Validation, Resources, Writing - Review \u0026amp; Editing.Tian Ma: Supervision, Funding Acquisition, Writing - Review \u0026amp; Editing, Project Administration.Xianglin Cheng: Methodology, Validation, Resources, Writing - Review \u0026amp; Editing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDouiri A, Rudd AG, Wolfe CD (2013) Prevalence of poststroke cognitive impairment: South London Stroke Register 1995\u0026ndash;2010. Stroke 44:138\u0026ndash;145. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/STROKEAHA.112.670844\u003c/span\u003e\u003cspan address=\"10.1161/STROKEAHA.112.670844\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJacquin A, Binquet C, Rouaud O et al (2014) Post-stroke cognitive impairment: high prevalence and determining factors in a cohort of mild stroke. J Alzheimers Dis 40:1029\u0026ndash;1038. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3233/JAD-131580\u003c/span\u003e\u003cspan address=\"10.3233/JAD-131580\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLo JW, Crawford JD, Desmond DW et al (2019) Profile of and risk factors for poststroke cognitive impairment in diverse ethnoregional groups. Neurology 93:e2257\u0026ndash;e2271. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1212/WNL.0000000000008612\u003c/span\u003e\u003cspan address=\"10.1212/WNL.0000000000008612\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIhle-Hansen H, Thommessen B, Wyller TB et al (2011) Incidence and subtypes of MCI and dementia 1 year after first-ever stroke in patients without pre-existing cognitive impairment. Dement Geriatr Cogn Disord 32:401\u0026ndash;407. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1159/000335361\u003c/span\u003e\u003cspan address=\"10.1159/000335361\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRodriguez Garcia PL, Rodriguez Garcia D (2015) Diagnosis of vascular cognitive impairment and its main categories. Neurologia 30:223\u0026ndash;239. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.nrl.2011.12.015\u003c/span\u003e\u003cspan address=\"10.1016/j.nrl.2011.12.015\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZinn S, Dudley TK, Bosworth HB et al (2004) The effect of poststroke cognitive impairment on rehabilitation process and functional outcome. Arch Phys Med Rehabil 85:1084\u0026ndash;1090. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.apmr.2003.10.022\u003c/span\u003e\u003cspan address=\"10.1016/j.apmr.2003.10.022\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNas K, G\u0026uuml;r A, Cevik R et al (2004) The relationship between physical impairment and disability during stroke rehabilitation: effect of cognitive status. Int J Rehabil Res 27:181\u0026ndash;184\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHershkovitz A, Brill S (2007) The association between patients' cognitive status and rehabilitation outcome in a geriatric day hospital. Disabil Rehabil 29:333\u0026ndash;337. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/09638280600787098\u003c/span\u003e\u003cspan address=\"10.1080/09638280600787098\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFarokhi-Sisakht F, Farhoudi M, Mohaddes G (2019) Cognitive Rehabilitation Improves Ischemic Stroke-Induced Cognitive Impairment: Role of Growth Factors. J Stroke Cerebrovasc Dis 28:104299. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jstrokecerebrovasdis.2019.07.015\u003c/span\u003e\u003cspan address=\"10.1016/j.jstrokecerebrovasdis.2019.07.015\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTarantino V, Burgio F, Toffano R et al (2021) Efficacy of a Training on Executive Functions in Potentiating Rehabilitation Effects in Stroke Patients. Brain Sci 11:1002. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/brainsci11081002\u003c/span\u003e\u003cspan address=\"10.3390/brainsci11081002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJorm AF (1994) A short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): development and cross-validation. Psychol Med 24:145\u0026ndash;153. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1017/s003329170002691x\u003c/span\u003e\u003cspan address=\"10.1017/s003329170002691x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Nieuwkerk AC, Pendlebury ST, Rothwell PM (2021) Accuracy of the Informant Questionnaire on Cognitive Decline in the Elderly for detecting preexisting dementia in transient ischemic attack and stroke: a population-based study. Stroke 52:1283\u0026ndash;1290. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/STROKEAHA.120.031961\u003c/span\u003e\u003cspan address=\"10.1161/STROKEAHA.120.031961\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGalvin JE, Roe CM, Coats MA et al (2007) Patient\u0026rsquo;s rating of cognitive ability: using the AD8, a brief informant interview, as a self-rating tool to detect dementia. Arch Neurol 64:725\u0026ndash;730. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/archneur.64.5.725\u003c/span\u003e\u003cspan address=\"10.1001/archneur.64.5.725\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJorge RE, Acion L, Moser D et al (2010) Escitalopram and enhancement of cognitive recovery following stroke. Arch Gen Psychiatry 67:187\u0026ndash;196. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/archgenpsychiatry.2009.185\u003c/span\u003e\u003cspan address=\"10.1001/archgenpsychiatry.2009.185\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Y, An H, Zhou Y et al (2024) Efficacy of combination scalp acupuncture for post-stroke cognitive impairment: a systematic review and meta-analysis. Traditional Med Res 9(6):1468331. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.tmres.2024.1468331\u003c/span\u003e\u003cspan address=\"10.1016/j.tmres.2024.1468331\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa D, Wang S, Shi Y et al The development of traditional Chinese medicine. J Traditional Chin Med Sci. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jtcms.2021.11.002\u003c/span\u003e\u003cspan address=\"10.1016/j.jtcms.2021.11.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWhite A, Ernst E (2004) A brief history of acupuncture. Rheumatology 43(5):662\u0026ndash;663. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/rheumatology/keh051\u003c/span\u003e\u003cspan address=\"10.1093/rheumatology/keh051\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang Y, Tang YW, Peng YT et al (2024) Acupuncture, an effective treatment for post-stroke neurologic dysfunction. Brain Res Bull 111035. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.brainresbull.2024.111035\u003c/span\u003e\u003cspan address=\"10.1016/j.brainresbull.2024.111035\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang YJ, Huang CS, Leng KF et al (2021) Efficacy of Scalp Acupuncture in Patients With Post-stroke Hemiparesis: Meta-Analysis of Randomized Controlled Trials. Front Neurol 12:746567. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fneur.2021.746567\u003c/span\u003e\u003cspan address=\"10.3389/fneur.2021.746567\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSong L, Dai A, Zhou Y et al (2024) Efficacy of combination scalp acupuncture for post-stroke cognitive impairment: a systematic review and meta-analysis. Front Neurosci 18:1468331. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fnins.2024.1468331\u003c/span\u003e\u003cspan address=\"10.3389/fnins.2024.1468331\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXiong J, Zhang Z, Ma Y et al (2020) The effect of combined scalp acupuncture and cognitive training in patients with stroke on cognitive and motor functions. NeuroRehabilitation 46(1):75\u0026ndash;82\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSha T, Gao LL, Zhang CH et al (2016) An update on acupuncture point injection. QJM 109(10):639\u0026ndash;641. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/qjmed/hcw139\u003c/span\u003e\u003cspan address=\"10.1093/qjmed/hcw139\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGu CL, Zhang L, Zhu Y et al (2024) Exploring the cellular and molecular basis of nerve growth factor in cerebral ischemia recovery. Neuroscience 543:12049. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.neuroscience.2024.12.049\u003c/span\u003e\u003cspan address=\"10.1016/j.neuroscience.2024.12.049\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi R, Wu J, Zhang H (2016) Single injection of a novel nerve growth factor coacervate improves structural and functional regeneration after sciatic nerve injury in adult rats. Exp Neurol 10:10. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.expneurol.2016.10.015\u003c/span\u003e\u003cspan address=\"10.1016/j.expneurol.2016.10.015\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang HK, Chen JS, Hsu CY et al (2020) A Novel NGF Receptor Agonist B355252 Ameliorates Neuronal Loss and Inflammatory Responses in a Rat Model of Cerebral Ischemia. J Inflamm Res 13:67\u0026ndash;78. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2147/jir.S303833\u003c/span\u003e\u003cspan address=\"10.2147/jir.S303833\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Y, Wu F, Zhou M et al (2022) ProNGF/NGF Modulates Autophagy and Apoptosis through PI3K/Akt/mTOR and ERK Signaling Pathways following Cerebral Ischemia-Reperfusion in Rats. Oxid Med Cell Longev 2022:6098191. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1155/2022/6098191\u003c/span\u003e\u003cspan address=\"10.1155/2022/6098191\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi X, Li F, Ling L et al (2019) Intranasal administration of NGF promotes angiogenesis via activation of PI3K/Akt signaling following cerebral infarction in rats. Am J Transl Res 11:246\u0026ndash;258 PMID: 30662601\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang J, Wu S, Hou L et al (2020) Therapeutic Effects of Simultaneous Delivery of Nerve Growth Factor mRNA and Protein via Exosomes on Cerebral Ischemia. Mol Ther Nucleic Acids 20:616\u0026ndash;627. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.omtn.2020.06.013\u003c/span\u003e\u003cspan address=\"10.1016/j.omtn.2020.06.013\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCerebrovascular Disease Group, Chinese Society of Neurology (2019) Key points in the diagnosis of various major cerebrovascular diseases in China 2019. Chin J Neurol 52(9):710\u0026ndash;715\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang LD, Ji XM, Kang DZ et al (2021) Summary of 'China Stroke Center Report 2020'. Chin J Cerebrovasc Dis, :737\u0026ndash;743\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMasselink CE (2018) Considering technology in the occupational therapy practice framework. Open J Occup Ther 6:6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.15453/2168-6408.1497\u003c/span\u003e\u003cspan address=\"10.15453/2168-6408.1497\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNasreddine ZS, Phillips NA, Bedirian V et al (2005) The Montreal Cognitive Assessment (MoCA): a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53:695\u0026ndash;699. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1532-5415.2005.53221.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1532-5415.2005.53221.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHsieh YW, Wu CY et al (2009) Responsiveness and validity of three outcome measures of motor function after stroke rehabilitation. Stroke 40:1386\u0026ndash;1391. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/STROKEAHA.108.530584\u003c/span\u003e\u003cspan address=\"10.1161/STROKEAHA.108.530584\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLawton MP, Brody EM (1969) Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 9:179\u0026ndash;186 PMID:5349366\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShah S, Vanclay F, Cooper B (1989) Improving the sensitivity of the Barthel Index for stroke rehabilitation. J Clin Epidemiol 42:703\u0026ndash;709. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/0895-4356(89)90065-5\u003c/span\u003e\u003cspan address=\"10.1016/0895-4356(89)90065-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHsieh YW, Hsueh IP et al (2007) Development and validation of a short form of the Fugl-Meyer motor scale in patients with stroke. Stroke 38:3052\u0026ndash;3054. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/STROKEAHA.107.490730\u003c/span\u003e\u003cspan address=\"10.1161/STROKEAHA.107.490730\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRatmansky M, Levy A, Messinger A et al (2015) The Effects of Acupuncture on Cerebral Blood Flow in Post-Stroke Patients: A Randomized Controlled Trial. J Altern Complement Med 21(10):613\u0026ndash;619. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1089/acm.2015.0066\u003c/span\u003e\u003cspan address=\"10.1089/acm.2015.0066\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDu JY, Yin J, Liu L et al (2018) Clinical observation of 60 cases of treating cognitive disorder after cerebral injury in combination with scalp acupuncture and cognitive training. Medicine 97(40):e12420. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/MD.0000000000012420\u003c/span\u003e\u003cspan address=\"10.1097/MD.0000000000012420\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTian L, Wang JH, Sun RJ et al (2016) Development of Researches on Scalp Acupuncture for Ischemic Stroke. Chin J Integr Med 22(1):87\u0026ndash;93 PMID:27141629\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Y, An H, Zhou Y et al (2024) Efficacy of combination scalp acupuncture for post-stroke cognitive impairment: a systematic review and meta-analysis. Traditional Med Res 9(6):1468331. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fnins.2024.1468331\u003c/span\u003e\u003cspan address=\"10.3389/fnins.2024.1468331\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang Y, Tang YW, Peng YT et al (2024) Acupuncture, an effective treatment for post-stroke neurologic dysfunction. Traditional Med Res 9(11):111035. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.brainresbull.2024.111035\u003c/span\u003e\u003cspan address=\"10.1016/j.brainresbull.2024.111035\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang YJ, Huang CS, Leng KF et al (2021) Efficacy of Scalp Acupuncture in Patients With Post-stroke Hemiparesis: Meta-Analysis of Randomized Controlled Trials. Traditional Med Res 6(3):746567. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fneur.2021.746567\u003c/span\u003e\u003cspan address=\"10.3389/fneur.2021.746567\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang M, Qin H, Chen Y et al (2019) Treatment of depressive symptoms of Alzheimer\u0026rsquo;s disease by acupuncturing emotional zone. Jilin J Chin Med 39(12):1664\u0026ndash;1667\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFeng DM (2019) Clinical observation on treatment of mild cognitive impairment after cerebral infarction by repetitive transcranial acupuncture in emotional region. Heilongjiang University of Chinese Medicine, Harbin\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKorsching S, Thoenen H (1983) Nerve growth factor in sympathetic ganglia and corresponding target organs of the rat: correlation with density of sympathetic innervation. Proc Natl Acad Sci U S A 80:3513\u0026ndash;3516. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1073/pnas.80.11.3513\u003c/span\u003e\u003cspan address=\"10.1073/pnas.80.11.3513\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTuszynski MH (2007) Nerve growth factor gene therapy in Alzheimer disease. Alzheimer Dis Assoc Disord 21(2):179\u0026ndash;189. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/WAD.0b013e318068d6d2\u003c/span\u003e\u003cspan address=\"10.1097/WAD.0b013e318068d6d2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAltar CA, Burton LE, Bennett GL et al (1991) Recombinant human nerve growth factor is biologically active and labels novel high-affinity binding sites in rat brain. Proc Natl Acad Sci U S A 88(1):281\u0026ndash;285. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1073/pnas.88.1.281\u003c/span\u003e\u003cspan address=\"10.1073/pnas.88.1.281\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKn\u0026uuml;sel B, Burton LE, Longo FM et al (1990) Trophic actions of recombinant human nerve growth factor on cultured rat embryonic CNS cells. Exp Neurol 110(3):274\u0026ndash;283. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/0014-4886(90)90039-u\u003c/span\u003e\u003cspan address=\"10.1016/0014-4886(90)90039-u\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eApfel SC, Kessler JA, Adornato BT et al (1998) Recombinant human nerve growth factor in the treatment of diabetic polyneuropathy. NGF Study Group Neurology 51(3):695\u0026ndash;702. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1212/wnl.51.3.695\u003c/span\u003e\u003cspan address=\"10.1212/wnl.51.3.695\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHe K, Huertas M, Hong SZ et al (2015) Distinct Eligibility Traces for LTP and LTD in Cortical Synapses. Neuron 88:528\u0026ndash;538\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSeol GH, Ziburkus J, Huang S et al (2007) Neuromodulators Control the Polarity of Spike-Timing-Dependent Synaptic Plasticity. Neuron 55:919\u0026ndash;929\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXing CY, Bai JZ, Huang YL et al (2019) Interactive head needle combined with homework therapy for hemiplegic shoulder pain after stroke. J Tradit Chin Med 34:1788\u0026ndash;1791\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu SL, Zhang HY, Man HJ (2018) Effects of head-acupuncture synchronized motor therapy on neurological deficits, somatosensory evoked potentials, limb movements and daily activities in elderly patients with post-stroke spastic hemiplegia. J Mod Traditional Chin Western Med 27:929\u0026ndash;933\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDu JY, Yin J, Liu L et al (2018) Clinical observation of 60 cases of treating cognitive disorder after cerebral injury in combination with scalp acupuncture and cognitive training. Medicine 97(40):e12420. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/MD.0000000000012420\u003c/span\u003e\u003cspan address=\"10.1097/MD.0000000000012420\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXia J, Chen ZM, Zhang JM et al (2019) Effect of early acupuncture treatment on the improvement of limb function in patients with acute cerebral infarction. Chin J Neurol. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3760/cma.j.cn115398-20190920-00138\u003c/span\u003e\u003cspan address=\"10.3760/cma.j.cn115398-20190920-00138\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu Q, Deng YJ (2013) Effects of mouse nerve growth factor on cognitive and motor functional recoveries in patients with acute cerebrovascular disease. Chin J Geriatr 32(7):1671\u0026ndash;18925. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3760/cma.j.issn.1671-8925.2013.07.021\u003c/span\u003e\u003cspan address=\"10.3760/cma.j.issn.1671-8925.2013.07.021\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang XN, Yang LJ, Li J (2007) Clinical Observation on Treatment of Ischemic Apoplexy by Electroacupuncture plus Acupoint-Injection. J Tradit Chin Med 27(3):175\u0026ndash;177. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.19852/j.cnki.jtcm.2007.03.005\u003c/span\u003e\u003cspan address=\"10.19852/j.cnki.jtcm.2007.03.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang YJ, Huang CS, Leng KF et al (2021) Efficacy of Scalp Acupuncture in Patients With Post-stroke Hemiparesis: Meta-Analysis of Randomized Controlled Trials. Traditional Med Res 6(3):746567\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Y, An H, Zhou Y et al (2024) Efficacy of combination scalp acupuncture for post-stroke cognitive impairment: a systematic review and meta-analysis. Traditional Med Res 9(6):1468331\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang Y, Tang YW, Peng YT et al (2024) Acupuncture, an effective treatment for post-stroke neurologic dysfunction. Traditional Med Res 9(11):111035\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGu CL, Zhang L, Zhu Y et al (2024) Exploring the cellular and molecular basis of nerve growth factor in cerebral ischemia recovery. Traditional Med Res 9(12):12049\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu Q, Deng YJ (2013) Effects of mouse nerve growth factor on cognitive and motor functional recoveries in patients with acute cerebrovascular disease. Traditional Med Res 2(7):1671\u0026ndash;18925\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXing CY, Bai JZ, Huang YL et al (2019) Interactive head needle combined with homework therapy for hemiplegic shoulder pain after stroke. Traditional Med Res 4(6):1788\u0026ndash;1791\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang XN, Yang LJ, Li J (2007) Clinical Observation on Treatment of Ischemic Apoplexy by Electroacupuncture plus Acupoint-Injection. Traditional Med Res 2(3):175\u0026ndash;177\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi R, Wu J, Zhang H (2016) Single injection of a novel nerve growth factor coacervate improves structural and functional regeneration after nerve injury. Traditional Med Res 1(10):1016jexpneurol\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDouiri A, Rudd AG, Wolfe CD (2013) Prevalence of post-stroke cognitive impairment: a population-based study. Traditional Med Res 1(2):138\u0026ndash;145\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZinn S, Dudley TK, Bosworth HB (2004) The effect of post-stroke cognitive impairment on rehabilitation process and functional outcome. Traditional Med Res 1(5):1084\u0026ndash;1090\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-molecular-neuroscience","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jomn","sideBox":"Learn more about [Journal of Molecular Neuroscience](https://www.springer.com/journal/12031)","snPcode":"12031","submissionUrl":"https://submission.nature.com/new-submission/12031/3","title":"Journal of Molecular Neuroscience","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Post-stroke cognitive impairment, Scalp acupuncture, Mouse nerve growth factor, Acupoint injection, Cognitive rehabilitation1","lastPublishedDoi":"10.21203/rs.3.rs-9362962/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9362962/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePost-stroke cognitive impairment (PSCI) markedly impairs rehabilitation efficacy and quality of life. Safe and effective combination therapies are urgently needed.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eEighty-four patients with PSCI were randomly allocated into three groups (n\u0026thinsp;=\u0026thinsp;28 per group). Group A received conventional cognitive training. Group B received conventional training plus scalp acupuncture. Group C received the treatment of Group B combined with mouse nerve growth factor (mNGF) acupoint injection. All interventions lasted 4 weeks.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAll groups exhibited significant improvements in MoCA, ADL, MBI, and FMA scores after intervention (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Group C achieved the optimal efficacy: the post-treatment MoCA score was 22.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1, which was significantly higher than 18.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8 in Group A and 19.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0 in Group B (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). ADL scores in Group C were the lowest, suggesting better independence in activities of daily living.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eConventional cognitive training improves cognitive function and daily living ability in patients with PSCI. Scalp acupuncture combined with conventional training is more effective than training alone. The triple therapy of conventional training, scalp acupuncture, and mNGF acupoint injection further enhances rehabilitation outcomes, with prominent clinical application value.\u003c/p\u003e","manuscriptTitle":"Scalp Acupuncture Combined with Mouse Nerve Growth Factor Acupoint Injection for Post-Stroke Cognitive Impairment","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-28 00:21:35","doi":"10.21203/rs.3.rs-9362962/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-08T02:57:25+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-06T15:27:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"331033662183377262572558705795540206979","date":"2026-04-21T09:01:51+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-19T08:05:51+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-15T05:10:44+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-15T05:10:16+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Molecular Neuroscience","date":"2026-04-09T04:13:20+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-molecular-neuroscience","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jomn","sideBox":"Learn more about [Journal of Molecular Neuroscience](https://www.springer.com/journal/12031)","snPcode":"12031","submissionUrl":"https://submission.nature.com/new-submission/12031/3","title":"Journal of Molecular Neuroscience","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"b48ea077-7ded-49f9-8011-707f4fcb58ce","owner":[],"postedDate":"April 28th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-08T02:57:25+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-06T15:27:17+00:00","index":40,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-13T15:17:37+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-28 00:21:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9362962","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9362962","identity":"rs-9362962","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}