Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, 430070, China.
Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
Neurochem Res. 2023 Aug;48(8):2320-2334. doi: 10.1007/s11064-023-03923-x. Epub 2023 Apr 5.
Stroke is characterized by the abrupt failure of blood flow to a specific brain region, resulting in insufficient supply of oxygen and glucose to the ischemic tissues. Timely reperfusion of blood flow can rescue dying tissue but can also lead to secondary damage to both the infarcted tissues and the blood-brain barrier, known as ischemia/reperfusion injury. Both primary and secondary damage result in biphasic opening of the blood-brain barrier, leading to blood-brain barrier dysfunction and vasogenic edema. Importantly, blood-brain barrier dysfunction, inflammation, and microglial activation are critical factors that worsen stroke outcomes. Activated microglia secrete numerous cytokines, chemokines, and inflammatory factors during neuroinflammation, contributing to the second opening of the blood-brain barrier and worsening the outcome of ischemic stroke. TNF-α, IL-1β, IL-6, and other microglia-derived molecules have been shown to be involved in the breakdown of blood-brain barrier. Additionally, other non-microglia-derived molecules such as RNA, HSPs, and transporter proteins also participate in the blood-brain barrier breakdown process after ischemic stroke, either in the primary damage stage directly influencing tight junction proteins and endothelial cells, or in the secondary damage stage participating in the following neuroinflammation. This review summarizes the cellular and molecular components of the blood-brain barrier and concludes the association of microglia-derived and non-microglia-derived molecules with blood-brain barrier dysfunction and its underlying mechanisms.
中风的特征是血液突然流向特定的大脑区域，导致缺血组织供氧和葡萄糖不足。及时恢复血液流动可以挽救濒死组织，但也会导致梗死组织和血脑屏障的继发性损伤，即缺血/再灌注损伤。原发性和继发性损伤都会导致血脑屏障的双相开放，导致血脑屏障功能障碍和血管源性水肿。重要的是，血脑屏障功能障碍、炎症和小胶质细胞激活是加重中风预后的关键因素。神经炎症期间，活化的小胶质细胞分泌大量细胞因子、趋化因子和炎症因子，导致血脑屏障的第二次开放，使缺血性中风的预后恶化。TNF-α、IL-1β、IL-6 和其他小胶质细胞衍生的分子已被证明参与了血脑屏障的破坏。此外，其他非小胶质细胞衍生的分子，如 RNA、HSP 和转运蛋白，也参与了缺血性中风后的血脑屏障破坏过程，要么在直接影响紧密连接蛋白和内皮细胞的原发性损伤阶段，要么在参与随后的神经炎症的继发性损伤阶段。本综述总结了血脑屏障的细胞和分子组成，并得出了小胶质细胞衍生和非小胶质细胞衍生的分子与血脑屏障功能障碍及其潜在机制的关联。
