小胶质细胞
白质
吞噬作用
基因敲除
医学
刺激
髓鞘
血脑屏障
神经科学
化学
炎症
病理
免疫学
生物
中枢神经系统
内科学
生物化学
磁共振成像
放射科
细胞凋亡
作者
Luo‐Qi Zhou,Yun‐Hui Chu,Minghao Dong,Sheng Yang,Man Chen,Yue Tang,Xiao‐Wei Pang,Yun‐Fan You,Long‐Jun Wu,Wei Wang,Chuan Qin,Dai‐Shi Tian
标识
DOI:10.1016/j.bbi.2024.04.014
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.
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