AUTHOR=Zhang Shenghang , Jin Tingting , Wang Lulu , Liu Weilin , Zhang Yuhao , Zheng Yi , Lin Yunjiao , Yang Minguang , He Xiaojun , Lin Huawei , Chen Lidian , Tao Jing 

TITLE=Electro-Acupuncture Promotes the Differentiation of Endogenous Neural Stem Cells via Exosomal microRNA 146b After Ischemic Stroke

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=14

YEAR=2020

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2020.00223

DOI=10.3389/fncel.2020.00223

ISSN=1662-5102

ABSTRACT=<p><bold>Background:</bold> Evidences indicate that exosomes-mediated delivery of microRNAs (miRNAs or miRs) is involved in the neurogenesis of stroke. This study was to investigate the role of exosomal miRNAs in non-drug therapy of electro-acupuncture (EA) regulating endogenous neural stem cells for stroke recovery.</p><p><bold>Methods:</bold> The model of focal cerebral ischemia and reperfusion in rats were established by middle cerebral artery occlusion (MCAO) and treated by EA. The exosomes were extracted from peri-ischemic striatum and identified by exosomal biomarkers, and detected differentially expressed miRNAs with microarray chip. Primary stem cells were cultured, and oxygen–glucose deprivation and reperfusion (OGD/R) was used to mimic vitro ischemic injury.</p><p><bold>Results:</bold> The levels of exosomal biomarkers TSG101 and CD81 were increased in peri-ischemic striatum after EA treatment, and we revealed 25 differentially expressed miRNAs in isolated exosomes, of which miR-146b was selected for further analysis, and demonstrated that EA increased miR-146b expression and its inhibitors could block the effects. Subsequently, we confirmed that EA upregulated miR-146b expression to promote neural stem cells differentiation into neurons in peri-ischemic striatum. <italic>In vitro</italic>, it was verified that OGD/R hindered neural stem cells differentiation, and miR-146b inhibitors furtherly suppressed its differentiation, simultaneously NeuroD1 was involved in neural stem cells differentiation into neurons. Moreover, <italic>in vivo</italic> we found EA promoted NeuroD1-mediated neural stem cells differentiation via miR-146b. In addition, EA also could improve neurological deficits through miR-146b after ischemic stroke.</p><p><bold>Conclusion:</bold> EA promotes the differentiation of endogenous neural stem cells via exosomal miR-146b to improve neurological injury after ischemic stroke.</p>