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Ldl-stimulated microglial activation exacerbates ischemic white matter damage

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资源类型：
Pubmed体系：
作者：
Zhou Luo-Qi[1] * ; Chu Yun-Hui[1] * ; Dong Ming-Hao[1] * ; Yang Sheng[1] ; Chen Man[1] ; Tang Yue[1] ; Pang Xiao-Wei[1] ; You Yun-Fan[1] ; Wu Long-Jun[2] ; Wang Wei[1] ; Qin Chuan[1] ; Tian Dai-Shi[1,3,4] ;
单位： [1]Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. [2]Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA. [3]Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China [4]Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
出处：
DOI： 10.1016/j.bbi.2024.04.014
ISSN：

关键词： Microglia White matter ischemia Low-density lipoprotein Lipid metabolism

摘要：
The role of microglia in triggering the blood-brain barrier (BBB) impairment and white matter damage after chronic cerebral hypoperfusion is unclear. Here we demonstrated that the vessel-adjacent microglia were specifically activated by the leakage of plasma low-density lipoprotein (LDL), which led to BBB breakdown and ischemic demyelination. Interestingly, we found that LDL stimulation enhanced microglial phagocytosis, causing excessive engulfment of myelin debris and resulting in an overwhelming lipid burden in microglia. Surprisingly, these lipid-laden microglia exhibited a suppressed profile of inflammatory response and compromised pro-regenerative properties. Microglia-specific knockdown of LDLR or systematic medication lowering circulating LDL-C showed protective effects against ischemic demyelination. Overall, our findings demonstrated that LDL-stimulated vessel-adjacent microglia possess a disease-specific molecular signature, characterized by suppressed regenerative properties, which is associated with the propagation of demyelination during ischemic white matter damage.Copyright © 2024. Published by Elsevier Inc.

基金：
Ministry of Science and Technology China Brain Initiative Grant 2022ZD0204704 (WW); National Natural Science Foundation of China 82271341 (CQ); National Natural Science Foundation of China 82301510 (LQZ); National Natural Science Foundation of China 82371404, 82071380 (DST); Knowledge Innovation Program of Wuhan Shuguang Project 2022020801020454 (CQ); Tongji Hospital (HUST) Foundation for Excellent Young Scientist 2020YQ06 (CQ); Tongji Hospital (HUST) Foundation for Excellent Young Scientist 24-2KYC13057- 12 (LQZ).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类 | 2 区 医学
小类 | 2 区 免疫学 2 区 神经科学 2 区 精神病学
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 神经科学 1 区 精神病学 2 区 免疫学
第一作者：
第一作者单位： [1]Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
共同第一作者：
通讯作者：
通讯机构： [1]Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. [3]Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China [4]Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
推荐引用方式(GB/T 7714)：
Zhou Luo-Qi,Chu Yun-Hui,Dong Ming-Hao,et al.Ldl-stimulated microglial activation exacerbates ischemic white matter damage[J].Brain, Behavior, And Immunity.2024,doi:10.1016/j.bbi.2024.04.014.
APA：
Zhou Luo-Qi,Chu Yun-Hui,Dong Ming-Hao,Yang Sheng,Chen Man...&Tian Dai-Shi.(2024).Ldl-stimulated microglial activation exacerbates ischemic white matter damage.Brain, Behavior, And Immunity,,
MLA：
Zhou Luo-Qi,et al."Ldl-stimulated microglial activation exacerbates ischemic white matter damage".Brain, Behavior, And Immunity .(2024)

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