中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (4): 825-831.doi: 10.4103/1673-5374.350698

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

迷走神经刺激是治疗缺血性脑卒中的潜在方法

  

  • 出版日期:2023-04-15 发布日期:2022-10-29
  • 基金资助:
    重庆市自然科学基金项目（cstc2019jcyj-msxmX0026）；重庆市医学科研项目（2021ZY023818）；重庆市自然科学基金项目（cstc2018jcyjAX0180）

Vagus nerve stimulation is a potential treatment for ischemic stroke

Yi-Lin Liu1, 2, San-Rong Wang1, Jing-Xi Ma3, 4, Le-Hua Yu1, *, Gong-Wei Jia1, *   

  1. 1Department of Rehabilitation, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China;  2The Second Clinical College, Chongqing Medical University, Chongqing, China;  3Department of Neurology, Chongqing General Hospital, Chongqing, China; 4Chongqing Key Laboratory of Neurodegenerative Diseases, Chongqing, China
  • Online:2023-04-15 Published:2022-10-29
  • Contact: Gong-Wei Jia, MD, jiagongwei@hospital.cqmu.edu.cn; Le-Hua Yu, MD, 300895@cqmu.edu.cn.
  • Supported by:
    This work was supported by the Natural Science Foundation of Chongqing, No. cstc2019jcyj-msxmX0026; the Medical Scientific Research Projects Foundation of Chongqing, No. 2021ZY023818, and the Natural Science Foundation of Chongqing, No. cstc2018jcyjAX0180 (all to GWJ). 

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摘要：

小胶质细胞是大脑的主要先天性免疫细胞，可在缺血性脑卒中后变得活跃并趋向促炎表型或调节表型。有研究认为迷走神经刺激可激活小胶质细胞的表型变化，并对脑缺血再灌注损伤产生神经保护作用。实验以大脑中动脉闭塞法建立缺血性脑卒中模型大鼠，30min后进行迷走神经刺激。（1）发，迷走神经刺激可促进缺血半暗带中小胶质细胞从促炎表型向调节表型的转变，通过激活α7烟碱乙酰胆碱受体的表达，降低促炎表型因子诱导型一氧化氮合成酶和肿瘤坏死因子α的水平及促进调节因子精氨酸酶1和转化生长因子β1的表达。（2）敲低α7烟碱乙酰胆碱受体表达可降低抑制Toll样受体4/核因子κB通路相关蛋白Toll样受体4和髓样分化因子88表达以及IκBα和核因子κB磷酸磷酸化水平，同时削弱迷走神经刺激对缺血性脑卒中的保护作用。（3）迷走神经刺激可能通过激活α7烟碱乙酰胆碱受体进而抑制Toll样受体4/核因子κB的表达，调控脑卒中后小胶质细胞极化，起到治疗缺血性脑卒中的作用的。实验结果证实了迷走神经刺激对缺血性脑卒中的作用机制。

https://orcid.org/0000-0002-9151-5207 (Gong-Wei Jia)

关键词: 迷走神经刺激, 脑缺血, 再灌注, 神经保护, 小胶质细胞, 促炎表型, 调节表型, α7烟碱乙酰胆碱受体, Toll样受体, 核因子κB

Abstract: Microglia are the brain’s primary innate immune cells, and they are activated and affect pro-inflammatory phenotype or regulatory phenotype after ischemic stroke. Vagus nerve stimulation was shown to activate microglial phenotypic changes and exhibit neuroprotective effects in ischemia/reperfusion injury. In this study, we established rat models of ischemic stroke by occlusion of the middle cerebral artery and performed vagus nerve stimulation 30 minutes after modeling. We found that vagus nerve stimulation caused a shift from a pro-inflammatory phenotype to a regulatory phenotype in microglia in the ischemic penumbra. Vagus nerve stimulation decreased the levels of pro-inflammatory phenotype markers inducible nitric oxide synthase and tumor necrosis factor α and increased the expression of regulatory phenotype markers arginase 1 and transforming growth factor β through activating α7 nicotinic acetylcholine receptor expression. Additionally, α7 nicotinic acetylcholine receptor blockade reduced the inhibition of Toll-like receptor 4/nuclear factor kappa-B pathway-associated proteins, including Toll-like receptor 4, myeloid differentiation factor 88, I kappa B alpha, and phosphorylated-I kappa B alpha, and also weakened the neuroprotective effects of vagus nerve stimulation in ischemic stroke. Vagus nerve stimulation inhibited Toll-like receptor 4/nuclear factor kappa-B expression through activating α7 nicotinic acetylcholine receptor and regulated microglial polarization after ischemic stroke, thereby playing a role in the treatment of ischemic stroke. Findings from this study confirm the mechanism underlying vagus nerve stimulation against ischemic stroke.

Key words: cerebral ischemia, microglia, neuroprotection, nuclear factor kappa-B, pro-inflammatory phenotype, regulatory phenotype, reperfusion, Toll-like receptor 4, vagus nerve stimulation, α7 nicotinic acetylcholine receptor