Electroacupuncture promotes axonal regrowth by attenuating the myelin-associated inhibitors-induced RhoA/ROCK pathway in cerebral ischemia/reperfusion rats

Schematic illustration of the mechanisms of EA in promoting axonal regeneration following cerebral ischemia/reperfusion. [Display omitted] •EA could improve neurological function and neuronal ultrastructure in cerebral I/R rats.•EA could improve the unfavorable milieu by regulating the expression of MAIs in cerebral I/R rats.•EA could weaken the inhibition of axonal regrowth by downregulating the RhoA/ROCK pathway in cerebral I/R rats.•EA could promote nerve regeneration through the upregulation of GAP43 and BDNF in cerebral I/R. The limited capacity of central nerve regeneration after cerebral ischemia has been the focus of attention in the field. Electroacupuncture (EA) is an effective therapy for functional rehabilitation after cerebral stroke. However, the underlying mechanism is still unclear. This study explored whether EA can improve the inhibitory microenvironment, attenuate RhoA/ROCK-mediated neurite regrowth inhibitory pathways, andpromote the expression of neuroplasticity proteins, thus exerting a protective role in cerebral ischemia/reperfusion (I/R) injury. Rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by 7 days of reperfusion, and they received EA or fasudil once daily for 7 days. The Garcia JH score, 2,3,5-triphenyltetrazolium chloride (TTC) staining, and transmission electron microscopy (TEM) were used to assess neural injury. The protein and mRNA levels of myelin-associated inhibitors (MAIs), RhoA/ROCK pathway-related molecules and neuroplasticity-related proteins were examined to explore the effect of EA on rats with cerebral I/R injury. We found that EA significantly decreased the infarct size and improved neurological function and hippocampal ultrastructure in the rats with cerebral ischemia/reperfusion (I/R) injury. EA ameliorates the inhibition of axonal regrowth and provides a protective role in functional rehabilitation after cerebral stroke by downregulating the MAI-induced RhoA/ROCK signaling pathway and by promoting the expression of GAP43 and BDNF to protect against cerebral I/R injury. Our findings provide a better understanding of the molecular mechanism underlying EA as an effective therapy for ischemic stroke.