Electroacupuncture enhances rehabilitation through miR-181b targeting PirB after ischemic stroke.

Bin Deng,Heng Zhou,Lize Xiong,Dandan Zhou,Zhi Ma,Fuhai Bai,Qiang Wang

doi:10.1038/srep38997

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.

Highlights

Might be closely associated with the down-regulation of Nogo-A and its receptor, NgR1, in the central nervous system (CNS)[20,21,22]
Bonferroni post hoc analyses showed that the amounts of biotionylated dextran amine (BDA)-positive CST axons on the middle and left sides of the spinal cord gray matter (C3–5) were significantly increased in the Middle cerebral artery occlusion (MCAO) +EA group compared with the Sham and MCAO groups (P < 0.05, Fig. 1a and c)
Post hoc analyses showed EA treatment significantly increased the number of these fibers detected ipsilateral to the injection site compared with that in the MCAO group (P < 0.05, Fig. 1a and d)

Summary

Introduction

Might be closely associated with the down-regulation of Nogo-A and its receptor, NgR1, in the central nervous system (CNS)[20,21,22]. Among the miRNAs with high levels of expression in the brain, those that regulate axon growth and target pirb mRNA in response to EA treatment for ischemic stroke need to be further explored. To address these questions, the present study aimed to determine the pivotal role of PirB in EA-produced rehabilitation against ischemic stroke, and to screen and investigate the potential miRNAs, which can directly regulate PirB expression in vivo and in vitro study. This study is the first to reveal that EA exerts therapeutic effects through inducing epigenetic changes to regulate its targets, such as the miR-181b/PirB/RhoA/GAP43 axis

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Results

Conclusion