TIPE2 attenuates neuroinflammation and brain injury through Bcl-2/Bax/ cleaved caspase-3 apoptotic pathways after intracerebral hemorrhage in mice

作者全名："Xia, Xiaohui; Wang, Shuai; Wu, Lirong; Li, Guoxing; Hou, Kaiwen; Yu, Anyong; Yang, Zhao"

作者地址："[Xia, Xiaohui; Yang, Zhao] Chongqing Med Univ, Yongchuan Hosp, Dept Neurosurg, Chongqing 402160, Peoples R China; [Wang, Shuai; Li, Guoxing; Hou, Kaiwen] Gen Hosp Western Theater Command, Dept Outpatient, Chengdu 610083, Sichuan, Peoples R China; [Wu, Lirong] Chongqing Hosp Tradit Chinese Med, Dept Neurol, Chongqing 400021, Peoples R China; [Yu, Anyong] Zunyi Med Univ, Affiliated Hosp, Dept Emergency, Zunyi 563003, Guizhou, Peoples R China"

通信作者："Yang, Z (通讯作者)，Chongqing Med Univ, Yongchuan Hosp, Dept Neurosurg, Chongqing 402160, Peoples R China.; Yu, AY (通讯作者)，Zunyi Med Univ, Affiliated Hosp, Dept Emergency, Zunyi 563003, Guizhou, Peoples R China."

来源：BRAIN RESEARCH BULLETIN

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000888294500001

JCR分区：Q2

影响因子：3.8

年份：2022

卷号：191

期号：　

开始页：1

结束页：8

文献类型：Article

关键词：TIPE2; Microglia; Neuroinflammation; ICH

摘要："Background: Intracerebral hemorrhage (ICH) is a serious disease with high mortality and morbidity, and effective treatment is limited. A large amount of evidence suggests that the inflammatory response contributes to sec-ondary brain damage following ICH. TIPE2 is an essential negative regulator of both innate and adaptive im-munity, and depletion of TIPE2 causes inflammatory disease. However, the possible role of TIPE2 following ICH has not been reported. Methods: In this study, we investigated TIPE2 levels and inflammation in microglia treated with erythrocyte lysate in vitro. In addition, we analyzed the role of Bcl-2/Bax/cleaved caspase-3 apoptotic pathways in ICH mice. Furthermore, we observed proinflammatory cytokine production, BBB disruption, cerebral water content and neurological damage in ICH mice. Results: We found that TIPE2 levels were significantly decreased in erythrocyte lysate-treated microglia compared to control microglia.Upregulation of TIPE2 decreased microglia activation and cytokine production and accelerated brain damage in ICH mice. Furthermore, upregulation of TIPE2 decreased the higher ratio of Blc-2/Bax and increased cleaved caspase-3 levels in ICH mice. In addition, upregulation of TIPE2 attenuated proinflammatory cytokine production, BBB disruption, and severe brain inflammation after ICH. Conclusion: These results demonstrated that TIPE2 was negatively correlated with the pathogenesis of ICH, which prevented brain injury and attenuated deleterious inflammatory responses following ICH. TIPE2 might serve as a novel target for ICH therapy."

基金机构："Science and Technology Research Program of Chongqing Municipal Education Commission [KJQN202000419, cstc2020jcyj-msxmX0442]"

基金资助正文：Funding This work was supported by the Science and Technology Research Program of Chongqing Municipal Education Commission (Grant No. KJQN202000419) and cstc2020jcyj-msxmX0442.