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

Frontiers in Cellular Neuroscience

Yuhao Zhang¹  Huawei Lin¹  Lidian Chen¹  Xiaojun He¹  Yi Zheng¹  Yunjiao Lin¹  Jing Tao¹  Lulu Wang¹  Tingting Jin¹  Weilin Liu²  Minguang Yang²  Shenghang Zhang³ 

[1] College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China;Fujian University of Traditional Chinese Medicine, The Academy of Rehabilitation Industry, Fuzhou, China;The 900 Hospital of the Joint Logistic Team, Fuzhou, China;

关键词: electro-acupuncture;    ischemic stroke;    neural stem cells;    exosomes;    MiR-146b;   

DOI  :  10.3389/fncel.2020.00223

来源: DOAJ

【 摘 要 】

Background: 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.Methods: 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.Results: 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. In vitro, 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, in vivo 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.Conclusion: EA promotes the differentiation of endogenous neural stem cells via exosomal miR-146b to improve neurological injury after ischemic stroke.

【 授权许可】

Unknown