Vav1 promotes inflammation and neuronal apoptosis in cerebral ischemia/reperfusion injury by upregulating microglial and NLRP3 inflammasome activation  

作　　者：Jing Qiu Jun Guo Liang Liu Xin Liu Xianhui Sun Huisheng Chen 

机构地区：[1]Department of Neurology,General Hospital of Northern Theater Command,Shenyang,Liaoning Province,China [2]Department of Neurology,Tangdu Hospital,Air Force Medical University,Xi’an,Shaanxi Province,China

出　　处：《Neural Regeneration Research》2023年第11期2436-2442,共7页中国神经再生研究（英文版）

基　　金：Natural Science Foundation of Liaoning Province (General Program),No.2017010825 (to JQ)。

摘　　要：Microglia,which are the resident macrophages of the central nervous system,are an important part of the inflammatory response that occurs after cerebral ischemia.Vav guanine nucleotide exchange factor 1(Vav1) is a guanine nucleotide exchange factor that is related to microglial activation.However,how Vav1 participates in the inflammato ry response after cerebral ischemia/reperfusion inj ury remains unclea r.In this study,we subjected rats to occlusion and repe rfusion of the middle cerebral artery and subjected the BV-2 mic roglia cell line to oxygen-glucose deprivatio n/reoxygenation to mimic cerebral ischemia/repe rfusion in vivo and in vitro,respectively.We found that Vav1 levels were increased in the brain tissue of rats subjected to occlusion and reperfusion of the middle cerebral arte ry and in BV-2 cells subjected to oxygen-glucose deprivation/reoxygenation.Silencing Vav1 reduced the cerebral infarct volume and brain water content,inhibited neuronal loss and apoptosis in the ischemic penumbra,and im p roved neurological function in rats subjected to occlusion and repe rfusion of the middle cerebral artery.Further analysis showed that Vav1 was almost exclusively localized to microglia and that Vav1 downregulation inhibited microglial activation and the NOD-like receptor pyrin 3(NLRP3) inflammasome in the ischemic penumbra,as well as the expression of inflammato ry facto rs.In addition,Vov1 knoc kdown decreased the inflammatory response exhibited by BV-2 cells after oxygen-glucose deprivation/reoxyge nation.Taken together,these findings show that silencing Vav1 attenuates inflammation and neuronal apoptosis in rats subjected to cerebral ischemia/repe rfusion through inhibiting the activation of mic roglia and NLRP3 inflammasome.

关 键 词：apoptosis cerebral ischemia/reperfusion inflammatory cytokines microglia microglial activation middle cerebral artery occlusion neuroprotection NLRP3 inflammasome oxygen-glucose deprivation/reoxygenation Vav1 

分 类 号：R743.3[医药卫生—神经病学与精神病学]