Loss of Wip1 aggravates brain injury after ischaemia/reperfusion by overactivating microglia  

作　　者：Feng Yan Xiang Cheng Ming Zhao Shenghui Gong Ying Han Liping Ding Di Wu Yumin Luo Wei Zuo Lingling Zhu Ming Fan Xunming Ji 

机构地区：[1]Beijing Institute of Brain Disorders,Laboratory of Brain Disorders,Ministry of Science and Technology,Collaborative Innovation Center for Brain Disorders,Capital Medical University,Beijing,China [2]Cerebrovascular Disease Research Laboratory,Xuanwu Hospital,Beijing,China [3]Institute of Military Cognition and Brain Sciences,Academy of Military Medical Sciences,Beijing,China [4]Department of Pharmacy,Peking Union Medical College Hospital,Dongcheng-qu,Beijing,China [5]Co-Innovation Center of Neuroregeneration,Nantong University,Nantong,China

出　　处：《Stroke & Vascular Neurology》2021年第3期344-351,共8页卒中与血管神经病学（英文）

基　　金：This study was funded by Incubation foundation of Capital Medical University(PYZ2018061);Nature and Sciences Foundation of China(81430044,81974183,81930054,82072104).

摘　　要：Background and purpose The inflammatory response mediated by microglia/macrophages is closely related to cerebral ischaemia/reperfusion injury.Wild-type p53-induced protein phosphatase 1(Wip1),a serine/threonine phosphatase,is expressed in various tissues.A growing number of reports have suggested that Wip1 is a negative regulator of inflammation in peripheral tissue;however,its role in the central nervous system(CNS)remains unclear.This study aimed to clarify whether Wip1 can inhibit CNS inflammation by regulating microglia/macrophage functions after ischaemic injury.Methods A model of middle cerebral artery occlusion and reperfusion was established in mice.CNS inflammation was simulated by lipopolysaccharide treatment of primary microglia.Laser speckle imaging was used to monitor regional cerebral blood flow.Behavioural outcomes were assessed with a TreadScan gait analysis system.TTC staining was used to evaluate the infarct volume,and western blotting and immunofluorescence staining were applied to detect the phenotypical transformation of microglia.ELISA was performed to detect the levels of inflammatory factors.Results Wip1 expression was increased after ischaemia/reperfusion.Wip1-knockout(KO)mice displayed more severe brain injury than wild-type mice,as indicated by aggravated motor dysfunction,greater brain infarct volumes and higher expression of inflammatory cytokines(interleukin-6 and tumour necrosis factor alpha)in the brain.We also found that Wip1 depletion increased microglial/macrophage activation in both in vitro and in vivo models,which all showed activation of microglia/macrophages.Lentivirus-Ppm1d reversed the injury induced by Wip1-KO.Conclusions Our results suggest that Wip1 may inhibit neuroinflammation by inhibiting microglial/macrophage activation after brain ischaemia/reperfusion injury.

关 键 词：INFLAMMATION REPERFUSION WIP1 

分 类 号：R651.15[医药卫生—外科学]