Ldl-stimulated microglial activation exacerbates ischemic white matter damage

Brain Behav Immun. 2024 Apr 16;119:416-430. doi: 10.1016/j.bbi.2024.04.014. Online ahead of print.ABSTRACTThe 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.PMID:38636563 | DOI:10.1016/j.bbi.2024.04.014

Source: Brain, Behavior, and Immunity - April 18, 2024 Category: Neurology Authors: Luo-Qi Zhou Yun-Hui Chu Ming-Hao Dong Sheng Yang Man Chen Yue Tang Xiao-Wei Pang Yun-Fan You Long-Jun Wu Wei Wang Chuan Qin Dai-Shi Tian Source Type: research