Circulating Brain-Derived Neurotrophic Factor as a potential biomarker in stroke: a Systematic review and Meta-analysis

Abstract Background Stroke, an acute cerebrovascular event, is a leading cause of disability, placing a significant psycho-socioeconomic burden worldwide. Neuroplasticity is adaptation and reorganization following neuronal damage. Brain-derived neurotrophic factor (BDNF) is a neurotrophin coordinating neuroplasticity after various neurological disorders such as stroke. Methods We conducted a systematic search in the main electronic medical databases through January 2021 and identified studies that measured blood levels of BDNF in patients with stroke. The primary aim was to compare BDNF levels between patients with stroke and healthy controls (HC). The secondary aims included investigation of (1) longitudinal changes in the BDNF levels post-stroke, (2) effects of physical training, (3) repeated transcranial magnetic stimulation (rTMS), and presence of depression on BDNF levels in patients with stroke. Results Among 6243 reviewed records from PubMed, Web of Science, and Scopus, 62 studies were eligible for inclusion. Subjects with stroke, n = 1856, showed lower BDNF levels compared to HC, n=1191 (SMD [95%CI] = -1.04 [-1.49 to -0.58]). No significant difference was detected in the level of BDNF through time points past stroke. BDNF levels were lower in the patients with depression compared to non-depressed subjects (SMD [95%CI] = -0.60 [-1.10 to -0.10]). Physical training had an immediate positive effect on the BDNF levels and not statistically significant effect in the long term; SMD [95%CI] = 0.49 [0.09 to 0.88]) and SMD [95%CI] = 0.02 [-0.43 to 0.47]). Lastly, rTMS showed no effect on the level of BDNF with 0.00 SMD. Conclusions This study confirms that stroke significantly affects the level of BDNF in various domains such as cognition, affect, and motor function. We believe that BDNF could be regarded as a valuable diagnostic biomarker for acute stroke and a potential prognostic biomarker for depression and cognitive deficits.