Abstract
Recent studies have demonstrated microRNAs (miRNAs) and proteins are beneficial to axon regeneration, which may be involved in Electroacupuncture (EA) therapy against stroke. In this study, we aimed to determine the pivotal role of PirB in EA-produced rehabilitation against ischemic stroke; and to screen and investigate the potential miRNAs directly regulating PirB expression. The results showed EA treatment enhanced axon regeneration and new projections from the corticospinal tract at 28 d after cerebral ischemic reperfusion injury of rats. Then, we found EA decreased pirb mRNA and PirB protein expression in the penumbra within 28 days after reperfusion. The reduction of PirB expression facilitated neurite outgrowth after oxygen-glucose deprivation injury. The miRNA microarray showed the level of twenty kinds of miRNAs changed in the penumbra after EA administration. The bioinformatics study and luciferase assay verified miR-181b directly regulated pirb mRNA expression. EA increased miR-181b levels in the penumbras, and improved neurobehavioral function rehabilitation through miR-181b direct targeting of pirb mRNA to regulate the expression of PirB, RhoA and GAP43. In conclusion, we provide the first evidence that EA enhances rehabilitation against stroke by regulating epigenetic changes to directly act on its targets, such as the miR-181b/PirB/RhoA/GAP43 axis, which is a novel mechanism of EA therapy.