Vagus nerve stimulation is a potential treatment for ischemic stroke

作者全名："Liu, Yi-Lin; Wang, San-Rong; Ma, Jing-Xi; Yu, Le-Hua; Jia, Gong-Wei"

作者地址："[Liu, Yi-Lin; Wang, San-Rong; Yu, Le-Hua; Jia, Gong-Wei] Chongqing Med Univ, Affiliated Hosp 2, Dept Rehabil, Chongqing, Peoples R China; [Liu, Yi-Lin] Chongqing Med Univ, Clin Coll 2, Chongqing, Peoples R China; [Ma, Jing-Xi] Chongqing Gen Hosp, Dept Neurol, Chongqing, Peoples R China; [Ma, Jing-Xi] Chongqing Key Lab Neurodegenerat Dis, Chongqing, Peoples R China"

通信作者："Yu, LH; Jia, GW (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Rehabil, Chongqing, Peoples R China."

来源：NEURAL REGENERATION RESEARCH

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000903723200027

JCR分区：Q2

影响因子：6.1

年份：2023

卷号：18

期号：4

开始页：825

结束页：831

文献类型：Article

关键词：cerebral ischemia; microglia; neuroprotection; nuclear factor kappa-B; pro-inflammatory phenotype; regulatory phenotype; reperfusion; Toll-like receptor 4; vagus nerve stimulation; alpha 7 nicotinic acetylcholine receptor

摘要："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 alpha and increased the expression of regulatory phenotype markers arginase 1 and transforming growth factor beta through activating alpha 7 nicotinic acetylcholine receptor expression. Additionally, alpha 7 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 alpha 7 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."

基金机构：Natural Science Foundation of Chongqing [cstc2018jcyjAX0180]; Medical Scientific Research Projects Foundation of Chongqing [2021ZY023818]

基金资助正文："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)."