HDAC3 inhibitor (BRD3308) modulates microglial pyroptosis and neuroinflammation through PPAR & gamma;/NLRP3/GSDMD to improve neurological function after intraventricular hemorrhage in mice

作者全名："Li, Yuanyou; Liu, Chang; Wang, Guoqing; Wang, Haoxiang; Liu, Xiaoyin; Huang, Cheng; Chen, Yaxing; Fan, Lingjie; Zhou, Liangxue; Tong, Aiping"

作者地址："[Li, Yuanyou; Wang, Guoqing; Wang, Haoxiang; Liu, Xiaoyin; Chen, Yaxing; Zhou, Liangxue] Sichuan Univ, West China Hosp, West China Med Sch, Dept Neurosurg, Chengdu, Peoples R China; [Huang, Cheng; Tong, Aiping] Sichuan Univ, West China Med Sch, State Key Lab Biotherapy, Chengdu, Peoples R China; [Liu, Chang] Chongqing Med Univ, Dept Neurosurg, Affiliated Hosp 1, Chongqing, Peoples R China; [Fan, Lingjie] Sichuan Univ, Coll Comp Sci, Chengdu, Peoples R China"

通信作者："Zhou, LX (通讯作者)，Sichuan Univ, West China Hosp, West China Med Sch, Dept Neurosurg, Chengdu, Peoples R China.; Tong, AP (通讯作者)，Sichuan Univ, West China Med Sch, State Key Lab Biotherapy, Chengdu, Peoples R China."

来源：NEUROPHARMACOLOGY

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001033680800001

JCR分区：Q1

影响因子：4.6

年份：2023

卷号：237

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Histone deacetylase 3; Neuroinflammation; Peroxisome proliferator-activated receptor & gamma;; Pyrin domain-containing protein 3; Intraventricular hemorrhage

摘要："Neuroinflammation plays a vital role in intraventricular hemorrhage (IVH). Excessive neuroinflammation after IVH can activate the inflammasome in the cell and accelerate the occurrence of pyroptosis in cells, produce more inflammatory mediators, increase cell death, and lead to neurological deficits. Previous studies have reported that BRD3308 (BRD), an inhibitor of histone deacetylation by histone deacetylase 3 (HDAC3), suppresses inflammation-induced apoptosis and exhibits anti-inflammatory properties. However, it is unclear how BRD reduces the occurrence of the inflammatory cascade. In this study, we stereotactically punctured the ventricles of male C57BL/6J mice and injected autologous blood via the tail vein to simulate ventricular hemorrhage. Magnetic resonance imaging was used to detect ventricular hemorrhage and enlargement. Our findings demonstrated that BRD treatment significantly improved neurobehavioral performance and decreased neuronal loss, microglial activation, and pyroptosis in the hippocampus after IVH. At the molecular level, this treatment upregulated the expression of peroxisome proliferator-activated receptor ? (PPAR?) and inhibited NLRP3mediated pyroptosis and inflammatory cytokines. Therefore, we concluded that BRD reduced pyroptosis and neuroinflammation and improve nerve function in part by activating the PPAR?/NLRP3/GSDMD signaling pathway. Our findings suggest a potential preventive role for BRD in IVH."

基金机构："Chinese National Natural Science Foundation [82073404]; Postdoctoral Foundation of West China Hospital of Sichuan University, China [2020HXBH160]"

基金资助正文："This work was supported by the Chinese National Natural Science Foundation Grant No. 82073404 and Postdoctoral Foundation of West China Hospital of Sichuan University, China, No. 2020HXBH160."