Loss of Wip1 aggravates brain injury after ischaemia/reperfusion by overactivating microglia
作者机构：Beijing Institute of Brain DisordersLaboratory of Brain DisordersMinistry of Science and TechnologyCollaborative Innovation Center for Brain DisordersCapital Medical UniversityBeijingChina Cerebrovascular Disease Research LaboratoryXuanwu HospitalBeijingChina Institute of Military Cognition and Brain SciencesAcademy of Military Medical SciencesBeijingChina Department of PharmacyPeking Union Medical College HospitalDongcheng-quBeijingChina Co-Innovation Center of NeuroregenerationNantong UniversityNantongChina
出 版 物：《Stroke & Vascular Neurology》 (卒中与血管神经病学（英文）)
年 卷 期：2021年第6卷第3期
页 面：344-351页
核心收录：
学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学]
基 金：This study was funded by Incubation foundation of Capital Medical University(PYZ2018061) Nature and Sciences Foundation of China(81430044,81974183,81930054,82072104)
主 题：inflammation reperfusion Wip1
摘 要：Background and purpose The inflammatory response mediated by microglia/macrophages is closely related to cerebral ischaemia/reperfusion ***-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 *** study aimed to clarify whether Wip1 can inhibit CNS inflammation by regulating microglia/macrophage functions after ischaemic *** A model of middle cerebral artery occlusion and reperfusion was established in *** inflammation was simulated by lipopolysaccharide treatment of primary *** speckle imaging was used to monitor regional cerebral blood *** outcomes were assessed with a TreadScan gait analysis *** staining was used to evaluate the infarct volume,and western blotting and immunofluorescence staining were applied to detect the phenotypical transformation of *** was performed to detect the levels of inflammatory *** Wip1 expression was increased after ischaemia/***1-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 *** also found that Wip1 depletion increased microglial/macrophage activation in both in vitro and in vivo models,which all showed activation of microglia/***-Ppm1d reversed the injury induced by *** Our results suggest that Wip1 may inhibit neuroinflammation by inhibiting microglial/macrophage activation after brain ischaemia/reperfusion injury.
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