Crosstalk between Inflammation and the BBB in Stroke.
Crosstalk between Inflammation and the BBB in Stroke.
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中风中炎症与血脑屏障之间的串扰
DOI：
10.2174/1570159x18666200620230321
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发表时间：
2020
影响因子：
5.3
通讯作者：
Han Z
中科院分区：
文献类型：
--
作者：
Huang Y;Chen S;Luo Y;Han Z
血脑屏障（BBB）位于中枢神经系统（CNS）与循环系统的界面处，对建立和维持中枢神经系统的微环境稳态起着重要作用。中风后血脑屏障的破坏会促进炎症反应，因为它使得白细胞、T细胞及其他免疫细胞能够通过细胞旁和跨细胞途径穿越血脑屏障，进而浸润中枢神经系统实质。白细胞有助于清除坏死组织和促进神经元恢复，但它们也会加重血脑屏障损伤并恶化中风后果，尤其是在延迟再灌注后。此外，星形胶质细胞终足的肿胀被认为与脑缺血后出现的“无复流”现象有关，即大血管再通后，血流无法恢复至毛细血管。周细胞的募集及其随后对内皮细胞（ECs）的包绕可减轻血脑屏障的破坏，这使得炎症细胞穿越血脑屏障成为一个动态过程。此外，中间神经元和血管周围的小胶质细胞也与内皮细胞、星形胶质细胞和周细胞相互作用，共同构成神经血管单元。脑缺血后血脑屏障衍生的因子会触发小胶质细胞的激活。在损伤后期，小胶质细胞持续与脑血管内皮细胞相互作用，并通过获得一种保护表型（这可能是通过释放小胶质细胞衍生的可溶性因子实现的），参与包括损伤后血管生成在内的修复机制。综上所述，我们综述了中风过程中炎症与血脑屏障之间动态的双向相互作用，并揭示了基于炎症与血脑屏障相互作用的靶向干预措施，这将为开发新的治疗策略提供新的思路。
The blood-brain barrier (BBB), which is located at the interface between the central nervous system (CNS) and the circulatory system, is instrumental in establishing and maintaining the microenvironmental homeostasis of the CNS. BBB disruption following stroke promotes inflammation by enabling leukocytes, T cells and other immune cells to migrate via both the paracellular and transcellular routes across the BBB and to infiltrate the CNS parenchyma. Leukocytes promote the removal of necrotic tissues and neuronal recovery, but they also aggravate BBB injury and exacerbate stroke outcomes, especially after late reperfusion. Moreover, the swelling of astrocyte endfeet is thought to contribute to the ‘no-reflow’ phenomenon observed after cerebral ischemia, that is, blood flow cannot return to capillaries after recanalization of large blood vessels. Pericyte recruitment and subsequent coverage of endothelial cells (ECs) alleviate BBB disruption, which causes the transmigration of inflammatory cells across the BBB to be a dynamic process. Furthermore, interneurons and perivascular microglia also make contacts with ECs, astrocytes and pericytes to establish the neurovascular unit. BBB-derived factors after cerebral ischemia triggered microglial activation. During the later stage of injury, microglia remain associated with brain ECs and contribute to repair mechanisms, including postinjury angiogenesis, by acquiring a protective phenotype, which possibly occurs through the release of microglia-derived soluble factors. Taken together, we reviewed dynamic and bidirectional crosstalk between inflammation and the BBB during stroke and revealed targeted interventions based on the crosstalk between inflammation and the BBB, which will provide novel insights for developing new therapeutic strategies.