Frontiers in Behavioral Neuroscience · Sep 11, 2026

Median nerve electrical stimulation promotes myelin regeneration through regulating miR-1-3p/BDNF/TrkB-MAPK pathway in a transient cerebral ischemia rat model

By Li R, Lu J, Zhang C et al.

Introduction Median nerve electrical stimulation (MNES) has emerged as a promising peripheral neuromodulatory strategy for improving motor recovery after ischemic stroke. Because the median nerve provides strong afferent input to central sensorimotor pathways, MNES may influence post-stroke neural repair beyond symptomatic motor modulation. However, the molecular mechanisms linking MNES to myelin repair remain unclear. Brain-derived neurotrophic factor (BDNF) is closely involved in neuronal survival, plasticity, and myelin remodeling, and bioinformatic analysis identified BDNF as a putative target of miR-1-3p. Therefore, this study investigated whether MNES-associated neurological recovery and myelin repair after ischemic stroke involve modulation of the miR-1-3p/BDNF/TrkB-MAPK pathway. Methods Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R), followed by MNES every other day for seven sessions. Neurological function, infarct injury, neuronal survival, neuroinflammation, myelin integrity, and pathway-related molecular changes were evaluated using behavioral, histological, ultrastructural, RT-qPCR, and Western blot analyses. Results MNES was associated with improved neurological performance, reduced infarct injury, better preservation of myelin structure, decreased miR-1-3p expression, and increased BDNF, TrkB, and MAPK expression. In miR-1-3p modulation experiments, miR-1-3p antagomir partially mimicked the neuroprotective and myelin-related effects observed after MNES, whereas miR-1-3p agomir attenuated several MNES-associated benefits and reduced BDNF/TrkB-MAPK pathway-related protein expression. Conclusion These findings suggest that MNES may support early neurological recovery and myelin repair after ischemic stroke, at least in part through involvement of the miR-1-3p/BDNF/TrkB-MAPK pathway. Further studies are required to confirm direct molecular targeting, long-term efficacy, safety, and translational relevance.

doi.org/10.3389/fnbeh.2026.1820913PubMed 42798493Interventions