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电针通过上调Notch1表达促进中风后大鼠齿状回神经干细胞增殖和神经发生。

Electroacupuncture promotes neural stem cell proliferation and neurogenesis in the dentate gyrus of rats following stroke via upregulation of Notch1 expression.

作者信息

Zhao Junhong, Sui Minghong, Lü Xiao, Jin Dongmei, Zhuang Zhiqiang, Yan Tiebin

机构信息

Department of Rehabilitation Medicine, Sun Yat‑sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.

出版信息

Mol Med Rep. 2015 Nov;12(5):6911-7. doi: 10.3892/mmr.2015.4279. Epub 2015 Sep 2.

Abstract

Neural stem cells (NSCs) are important in rehabilitation following stroke. Electroacupuncture (EA) treatment has been observed to promote the recovery of neurological functions subsequent to stroke, however, the effects of EA on the proliferation and differentiation of NSCs and its potential mechanisms remain to be elucidated. In the present study, rats, in which a stroke was induced through middle cerebral artery occlusion (MCAO), were treated with EA or control manipulation for 21 days. The modified Neurological Severity score and Morris water maze tests were used to assess the neurological functions of the rats. Bromodeoxyuridine (BrdU)/glial fibrillary acidic protein (GFAP) or BrdU/neuronal marker (NeuN) double immunofluorescence staining were used to examine the proliferation and differentiation of the NSCs. Reverse transcription quantitative polymerase chain reaction (RT‑qPCR) and western blot analyses were performed to detect the expression levels of Notch1 and Hes1 in the dentate gyrus (DG) of the hippocampus of rats following MCAO. The results demonstrated that EA treatment significantly improved the neurological functional recovery of rats following stroke. A significant increase was observed in the number of BrdU+/GAFP+ and BrdU+/NeuN+ cells in the DG area in the EA‑treated rats compared with that of the control group. RT‑qPCR analysis revealed that EA treatment significantly increased the expression levels of Notch1 and Hes1, which may account for the enhanced proliferation and differentiation of NSCs. In conclusion, to the best of our knowledge, the present study was the first to demonstrate that EA treatment promoted NSC proliferation and neurogenesis in the DG area through the upregulation of Notch signaling following a stroke; therefore, EA may be a useful novel therapeutic strategy in future stroke treatment.

摘要

神经干细胞(NSCs)在中风后的康复过程中具有重要作用。已有研究观察到,电针(EA)治疗可促进中风后神经功能的恢复,然而,EA对NSCs增殖和分化的影响及其潜在机制仍有待阐明。在本研究中,通过大脑中动脉闭塞(MCAO)诱导中风的大鼠接受EA或对照操作治疗21天。采用改良的神经功能评分和莫里斯水迷宫试验评估大鼠的神经功能。使用溴脱氧尿苷(BrdU)/胶质纤维酸性蛋白(GFAP)或BrdU/神经元标志物(NeuN)双重免疫荧光染色检测NSCs的增殖和分化。进行逆转录定量聚合酶链反应(RT-qPCR)和蛋白质免疫印迹分析,以检测MCAO后大鼠海马齿状回(DG)中Notch1和Hes1的表达水平。结果表明,EA治疗可显著改善中风后大鼠的神经功能恢复。与对照组相比,EA治疗组大鼠DG区BrdU+/GAFP+和BrdU+/NeuN+细胞数量显著增加。RT-qPCR分析显示,EA治疗可显著增加Notch1和Hes1的表达水平,这可能是NSCs增殖和分化增强的原因。总之,据我们所知,本研究首次证明EA治疗可通过中风后上调Notch信号通路促进DG区NSCs增殖和神经发生;因此,EA可能是未来中风治疗中一种有用的新治疗策略。

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