Cerebrolysin, Hemorrhagic Transformation, and Anticoagulation Timing after Reperfusion Therapy in Stroke: Secondary Analysis of the CEREHETIS Trial

Cerebrolysin, Hemorrhagic Transformation, and Anticoagulation Timing after Reperfusion Therapy in Stroke: Secondary Analysis of the CEREHETIS Trial | 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 Cerebrolysin, Hemorrhagic Transformation, and Anticoagulation Timing after Reperfusion Therapy in Stroke: Secondary Analysis of the CEREHETIS Trial Mikhail N. Kalinin, Dina R. Khasanova This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5101232/v2 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Jan, 2026 Read the published version in Frontiers in Pharmacology → Version 2 posted You are reading this latest preprint version Show more versions Abstract Background The timing of anticoagulation resumption after ischemic stroke remains uncertain, especially in patients at high risk of hemorrhagic transformation (HT). Although Cerebrolysin reduces HT incidence, its impact on dynamic risk evolution and the safe therapeutic window is unknown. Methods This post-hoc survival analysis of the CEREHETIS trial ( ISRCTN87656744 ) included 238 patients with middle cerebral artery infarction, stratified into low (HTI = 0) and high (HTI = 1–4) HT-risk groups. Temporal hazard dynamics over 14 days were modeled with the Gompertz distribution. Nonlinear hazard acceleration (NLHA) and the compounding effect—capturing self-amplifying instantaneous risk—were quantified to locate the inception point when hazard stabilization allows safe anticoagulation. A conservative NLHA threshold (5 % of peak = 0.23 % per day) defined this risk-equilibrium. Results In high-risk patients, Cerebrolysin significantly reduced hazards of symptomatic HT (HR = 0.245; 95 % CI 0.072–0.837; p = 0.020) and any HT (HR = 0.543; 95 % CI 0.297–0.991; p = 0.032). In controls, the compounding effect peaked on day 1 and persisted through day 3, whereas Cerebrolysin markedly attenuated this amplification and shortened the hazardous period. Inception points occurred on days 2–3 with Cerebrolysin versus days 4–5 in controls. In low-risk patients, both groups achieved constant hazard by day 2. Conclusion Cerebrolysin mitigates nonlinear hazard amplification, lowers HT risk, and advances the risk-equilibrium point by 1–2 days, enabling earlier and safer anticoagulation resumption and supporting a hazard-based, individualized approach to post-stroke management. Cerebrolysin Hemorrhagic Transformation Stroke Reperfusion Therapy Anticoagulation Timing Survival Analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Full Text Additional Declarations The authors declare no competing interests. Supplementary Files Rawdatasheet.xlsx Statacode.pdf Statacode.pdf Cite Share Download PDF Status: Published Journal Publication published 05 Jan, 2026 Read the published version in Frontiers in Pharmacology → Version 2 posted You are reading this latest preprint version Show more versions 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-5101232","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":367802761,"identity":"b7810d44-157a-4d7b-803e-8337815aaf9a","order_by":0,"name":"Mikhail N. Kalinin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuUlEQVRIiWNgGAWjYDACZgaGAw8YEuRAbCCDWC0JDAnGYC0JRNsE1JLYAGEQAczZeQ8eSKhJS58fdvgh0BY7Od0GAlosm/kSDiQcy8ndeDvNAKgl2djsAAEtBod5gCrZKnI3zk4AaTmQuI04Lf8q0g1np38gQUtiW06CvHQOKbYk9qUZbpDOKTiQYECMX86fMf7w4VuyvPzs9M0fPlTYyRHUgtALVmlArHIQkG8gRfUoGAWjYBSMKAAAXBxJFDymZBMAAAAASUVORK5CYII=","orcid":"","institution":"Kazan State Medical University","correspondingAuthor":true,"prefix":"","firstName":"Mikhail","middleName":"N.","lastName":"Kalinin","suffix":""},{"id":367802762,"identity":"0e57f990-308e-4743-af49-884f9cc21b97","order_by":1,"name":"Dina R. Khasanova","email":"","orcid":"","institution":"Kazan State Medical University","correspondingAuthor":false,"prefix":"","firstName":"Dina","middleName":"R.","lastName":"Khasanova","suffix":""}],"badges":[],"createdAt":"2024-09-17 07:10:01","currentVersionCode":2,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-5101232/v2","doiUrl":"https://doi.org/10.21203/rs.3.rs-5101232/v2","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.3389/fphar.2025.1725255","type":"published","date":"2026-01-06T00:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":94599158,"identity":"aae3091b-b0a0-44d2-ab25-75f4474dbdf3","added_by":"auto","created_at":"2025-10-28 19:03:27","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":294517,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 1.\u003c/strong\u003e Analytical framework for assessing hazard dynamics of HT to determine the optimal timing for anticoagulation resumption.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5101232/v2/e0a1246894befccb2a12dbcc.png"},{"id":94599300,"identity":"bdbd2763-19f1-49dc-b02f-cf1dc98498c4","added_by":"auto","created_at":"2025-10-28 19:05:01","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":986372,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 2.\u003c/strong\u003e Study flow chart.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5101232/v2/42956024cb61765f0067f773.png"},{"id":94599604,"identity":"21f7bbe1-c680-4839-91eb-aedbe03cb6d7","added_by":"auto","created_at":"2025-10-28 19:06:45","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":213968,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 3. \u003c/strong\u003eNon-parametric and parametric analysis. Standardized survival curves (dashed and solid lines) of the Gompertz model overlaid on Kaplan–Meier survival estimates (very-short-dashed and short-dashed lines represent low (HTI = 0) and high (HTI = 1–4) HT risk subgroups, respectively). Panel \u003cstrong\u003eA\u003c/strong\u003e: Symptomatic hemorrhagic transformation. Panel \u003cstrong\u003eB\u003c/strong\u003e: Any hemorrhagic transformation.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-5101232/v2/9c8e90b0dfb31c22011948f4.png"},{"id":94599771,"identity":"738e2975-1596-4be0-a3d8-c6d7200b1acb","added_by":"auto","created_at":"2025-10-28 19:07:47","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":184431,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 4.\u003c/strong\u003e Comparison of semiparametric Cox proportional hazards and time-dependent models with parametric Gompertz models, estimated with and without the ancillary γ-parameter. Regression coefficients are shown with 95% confidence intervals. Panel \u003cstrong\u003eA\u003c/strong\u003e: Symptomatic hemorrhagic transformation. Panel \u003cstrong\u003eB\u003c/strong\u003e: Any hemorrhagic transformation.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-5101232/v2/b65d60b6b7442d4e4e8d6bf3.png"},{"id":94599542,"identity":"a07f7f8f-d3df-42b4-82ab-2e434cb4c346","added_by":"auto","created_at":"2025-10-28 19:06:15","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":381857,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 5. \u003c/strong\u003eModel selection. The Nelson–Aalen cumulative hazard (navy) is overlaid on the Cox–Snell residuals (maroon). The Gompertz model is identified as the best fit based on the lowest Akaike (AIC) and Bayesian (BIC) information criteria values, as well as its similarity to the Cox proportional hazards model. Panel \u003cstrong\u003eA\u003c/strong\u003e: Symptomatic hemorrhagic transformation. Panel \u003cstrong\u003eB\u003c/strong\u003e: Any hemorrhagic transformation.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-5101232/v2/4a7a03f1ed3404a784fc52b9.png"},{"id":94599198,"identity":"5a17c45b-261b-4eee-8b7a-8ce2b55826c3","added_by":"auto","created_at":"2025-10-28 19:04:00","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":252077,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 6. \u003c/strong\u003eCerebrolysin treatment effects: Differences in standardized restricted mean survival time (RMST) curves between Cerebrolysin and control groups, with 95% confidence intervals. Panel \u003cstrong\u003eA\u003c/strong\u003e: Symptomatic hemorrhagic transformation. Panel \u003cstrong\u003eB\u003c/strong\u003e: Any hemorrhagic transformation.\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-5101232/v2/1b555f014ee371c28686b476.png"},{"id":94599203,"identity":"ab1aceff-ba7e-4a1e-bb3c-b78a9230c7ed","added_by":"auto","created_at":"2025-10-28 19:04:04","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":236956,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 7. \u003c/strong\u003eCerebrolysin treatment effects: Differences in standardized survival curves (absolute risk reduction) between the Cerebrolysin and control groups, with 95% confidence intervals. Panel \u003cstrong\u003eA\u003c/strong\u003e: Symptomatic hemorrhagic transformation. Panel \u003cstrong\u003eB\u003c/strong\u003e: Any hemorrhagic transformation.\u003c/p\u003e","description":"","filename":"Figure7.png","url":"https://assets-eu.researchsquare.com/files/rs-5101232/v2/a206d6dd7b8656ce23a2bac9.png"},{"id":94599773,"identity":"d544b273-e265-47e5-9c4e-8846bccd7bc3","added_by":"auto","created_at":"2025-10-28 19:07:48","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":224172,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 8. \u003c/strong\u003eCerebrolysin treatment effects: Number needed to treat (NNT) based on differences in standardized survival curves, with 95% confidence intervals. Panel \u003cstrong\u003eA\u003c/strong\u003e: Symptomatic hemorrhagic transformation. Panel \u003cstrong\u003eB\u003c/strong\u003e: Any hemorrhagic transformation.\u003c/p\u003e","description":"","filename":"Figure8.png","url":"https://assets-eu.researchsquare.com/files/rs-5101232/v2/69a7f15d3d2c3afb33fb314f.png"},{"id":94599633,"identity":"9f8c81e9-4d9a-42c6-bf75-7342cecb6c1f","added_by":"auto","created_at":"2025-10-28 19:06:51","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":284707,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 9.\u003c/strong\u003e Determining the timing of anticoagulation resumption. The analysis period is truncated at day 7, as the hazard dynamics approach near-zero values thereafter. The threshold is set at 0.23% per day. Solid lines represent mean estimates, and dashed lines denote 95% CI lower bounds. Panel \u003cstrong\u003eA\u003c/strong\u003e: Hazard dynamics in the most vulnerable subgroup—control patients with high HT risk (HTI = 1–4). Panel \u003cstrong\u003eB\u003c/strong\u003e: Standardized nonlinear hazard acceleration (NLHA) curves. For clarity, mean curves for patients with low HT risk are omitted.\u003c/p\u003e","description":"","filename":"Figure9.png","url":"https://assets-eu.researchsquare.com/files/rs-5101232/v2/553037ef168cce7a99068d78.png"},{"id":94599287,"identity":"664ff2ea-a34c-4283-8aa3-c08ecc2064db","added_by":"auto","created_at":"2025-10-28 19:04:54","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":337309,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 10.\u003c/strong\u003e Compounding effect estimated using the quadratic hazard function \u0026nbsp;\u003cem\u003eh\u003c/em\u003e(\u003cem\u003et\u003c/em\u003e)\u003csup\u003e2\u003c/sup\u003e with 95% confidence intervals. For visualization, the curves were log-transformed. The horizontal dotted line denotes the threshold (0.23% per day), and the vertical dotted lines indicate inception points for patients with high HT risk. Solid lines represent mean estimates, and shaded areas denote 95% confidence intervals. The dashed green line corresponds to the 95% CI lower bound of nonlinear hazard acceleration (NLHA). A compounding effect above the threshold line is considered clinically relevant. Panel \u003cstrong\u003eA\u003c/strong\u003e: Control group. Panel \u003cstrong\u003eB\u003c/strong\u003e: Cerebrolysin group.\u003c/p\u003e","description":"","filename":"Figure10.png","url":"https://assets-eu.researchsquare.com/files/rs-5101232/v2/cb7f1d6f2829464e833a61ab.png"},{"id":99727448,"identity":"48e68d4e-1625-4efa-bbd0-e25a01609ec9","added_by":"auto","created_at":"2026-01-07 16:51:14","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4045045,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript40.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5101232/v2_covered_61bbf865-e19e-4c7a-a42b-8b55066fc51f.pdf"},{"id":94599772,"identity":"b845f5b2-992d-4247-a522-d2749b1f3327","added_by":"auto","created_at":"2025-10-28 19:07:47","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":24608,"visible":true,"origin":"","legend":"","description":"","filename":"Rawdatasheet.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5101232/v2/b2a973bb96bc8bba858aacac.xlsx"},{"id":94599488,"identity":"a979957b-85b6-4a8a-9aa5-6d5d0c08d121","added_by":"auto","created_at":"2025-10-28 19:06:05","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":278494,"visible":true,"origin":"","legend":"","description":"","filename":"Statacode.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5101232/v2/8ff8de96f5a4cba53e83cd9a.pdf"},{"id":94599283,"identity":"7fbd53c9-164a-4484-af7b-982de11f9804","added_by":"auto","created_at":"2025-10-28 19:04:52","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":263456,"visible":true,"origin":"","legend":"","description":"","filename":"Statacode.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5101232/v2/e37c6204fa286753ef5a1178.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"Cerebrolysin, Hemorrhagic Transformation, and Anticoagulation Timing after Reperfusion Therapy in Stroke: Secondary Analysis of the CEREHETIS Trial","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Cerebrolysin, Hemorrhagic Transformation, Stroke, Reperfusion Therapy, Anticoagulation Timing, Survival Analysis","lastPublishedDoi":"10.21203/rs.3.rs-5101232/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5101232/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe timing of anticoagulation resumption after ischemic stroke remains uncertain, especially in patients at high risk of hemorrhagic transformation (HT). Although Cerebrolysin reduces HT incidence, its impact on dynamic risk evolution and the safe therapeutic window is unknown.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis \u003cem\u003epost-hoc\u003c/em\u003e survival analysis of the CEREHETIS trial (\u003ca href=\"https://doi.org/10.1186/ISRCTN87656744\"\u003eISRCTN87656744\u003c/a\u003e) included 238 patients with middle cerebral artery infarction, stratified into low (HTI = 0) and high (HTI = 1–4) HT-risk groups. Temporal hazard dynamics over 14 days were modeled with the Gompertz distribution. Nonlinear hazard acceleration (NLHA) and the compounding effect—capturing self-amplifying instantaneous risk—were quantified to locate the inception point when hazard stabilization allows safe anticoagulation. A conservative NLHA threshold (5 % of peak = 0.23 % per day) defined this risk-equilibrium.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn high-risk patients, Cerebrolysin significantly reduced hazards of symptomatic HT (HR = 0.245; 95 % CI 0.072–0.837; \u003cem\u003ep\u003c/em\u003e = 0.020) and any HT (HR = 0.543; 95 % CI 0.297–0.991; \u003cem\u003ep\u003c/em\u003e = 0.032). In controls, the compounding effect peaked on day 1 and persisted through day 3, whereas Cerebrolysin markedly attenuated this amplification and shortened the hazardous period. Inception points occurred on days 2–3 with Cerebrolysin versus days 4–5 in controls. In low-risk patients, both groups achieved constant hazard by day 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCerebrolysin mitigates nonlinear hazard amplification, lowers HT risk, and advances the risk-equilibrium point by 1–2 days, enabling earlier and safer anticoagulation resumption and supporting a hazard-based, individualized approach to post-stroke management.\u003c/p\u003e","manuscriptTitle":"Cerebrolysin, Hemorrhagic Transformation, and Anticoagulation Timing after Reperfusion Therapy in Stroke: Secondary Analysis of the CEREHETIS Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2025-10-28 18:36:02","doi":"10.21203/rs.3.rs-5101232/v2","editorialEvents":[{"type":"communityComments","content":1}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2024-10-18 18:41:32","doi":"10.21203/rs.3.rs-5101232/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5e3904bb-28f0-49aa-bb48-bed807c738fd","owner":[],"postedDate":"October 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-07T16:50:59+00:00","versionOfRecord":{"articleIdentity":"rs-5101232","link":"https://doi.org/10.3389/fphar.2025.1725255","journal":{"identity":"frontiers-in-pharmacology","isVorOnly":true,"title":"Frontiers in Pharmacology"},"publishedOn":"2026-01-06 00:00:00","publishedOnDateReadable":"January 6th, 2026"},"versionCreatedAt":"2025-10-28 18:36:02","video":"","vorDoi":"10.3389/fphar.2025.1725255","vorDoiUrl":"https://doi.org/10.3389/fphar.2025.1725255","workflowStages":[]},"version":"v2","identity":"rs-5101232","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5101232","identity":"rs-5101232","version":["v2"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}