Rui Li, Jingyi Lu, Chengcai Zhang, Xiaowei Zhang, Meiqi Wang, Ping Zhang, Kunli Yang, Hongmei Fang, Ying Gao, Kistina Mohamed, Che Ismail Che Noh, Yi Li, Kai Ling Chin
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.
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.