Cheng Jialin, Zheng Yuxiao, Cheng Fafeng, Wang Chunyu, Han Jinhua, Zhang Haojia, Lan Xin, Zhang Chuxin, Wang Xueqian, Wang Qingguo, Li Changxiang
College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
Neural Regen Res. 2026 Apr 1;21(4):1359-1372. doi: 10.4103/NRR.NRR-D-24-01417. Epub 2025 Jun 19.
Ischemic stroke, a frequently occurring form of stroke, is caused by obstruction of cerebral blood flow, which leads to ischemia, hypoxia, and necrosis of local brain tissue. After ischemic stroke, both astrocytes and the blood-brain barrier undergo morphological and functional transformations. However, the interplay between astrocytes and the blood-brain barrier has received less attention. This comprehensive review explores the physiological and pathological morphological and functional changes in astrocytes and the blood-brain barrier in ischemic stroke. Post-stroke, the structure of endothelial cells and peripheral cells undergoes alterations, causing disruption of the blood-brain barrier. This disruption allows various pro-inflammatory factors and chemokines to cross the blood-brain barrier. Simultaneously, astrocytes swell and primarily adopt two phenotypic states: A1 and A2, which exhibit different roles at different stages of ischemic stroke. During the acute phase, A1 reactive astrocytes secrete vascular endothelial growth factor, matrix metalloproteinases, lipid carrier protein-2, and other cytokines, exacerbating damage to endothelial cells and tight junctions. Conversely, A2 reactive astrocytes produce pentraxin 3, Sonic hedgehog, angiopoietin-1, and other protective factors for endothelial cells. Furthermore, astrocytes indirectly influence blood-brain barrier permeability through ferroptosis and exosomes. In the middle and late (recovery) stages of ischemic stroke, A1 and A2 astrocytes show different effects on glial scar formation. A1 astrocytes promote glial scar formation and inhibit axon growth via glial fibrillary acidic protein, chondroitin sulfate proteoglycans, and transforming growth factor-β. In contrast, A2 astrocytes facilitate axon growth through platelet-derived growth factor, playing a crucial role in vascular remodeling. Therefore, enhancing our understanding of the pathological changes and interactions between astrocytes and the blood-brain barrier is a vital therapeutic target for preventing further brain damage in acute stroke. These insights may pave the way for innovative therapeutic strategies for ischemic stroke.
缺血性中风是中风的一种常见形式，由脑血流阻塞引起，导致局部脑组织缺血、缺氧和坏死。缺血性中风后，星形胶质细胞和血脑屏障都会发生形态和功能转变。然而，星形胶质细胞与血脑屏障之间的相互作用却较少受到关注。这篇综述探讨了缺血性中风中星形胶质细胞和血脑屏障的生理和病理形态及功能变化。中风后，内皮细胞和外周细胞的结构发生改变，导致血脑屏障破坏。这种破坏使各种促炎因子和趋化因子能够穿过血脑屏障。同时，星形胶质细胞肿胀并主要呈现两种表型状态：A1和A2，它们在缺血性中风的不同阶段发挥不同作用。在急性期，A1反应性星形胶质细胞分泌血管内皮生长因子、基质金属蛋白酶、脂质运载蛋白-2等细胞因子，加剧对内皮细胞和紧密连接的损伤。相反，A2反应性星形胶质细胞产生五聚体3、音猬因子、血管生成素-1等对内皮细胞的保护因子。此外，星形胶质细胞通过铁死亡和外泌体间接影响血脑屏障通透性。在缺血性中风的中晚期（恢复）阶段，A1和A2星形胶质细胞对胶质瘢痕形成表现出不同影响。A1星形胶质细胞通过胶质纤维酸性蛋白、硫酸软骨素蛋白聚糖和转化生长因子-β促进胶质瘢痕形成并抑制轴突生长。相比之下，A2星形胶质细胞通过血小板衍生生长因子促进轴突生长，在血管重塑中起关键作用。因此，加深对星形胶质细胞与血脑屏障之间病理变化及相互作用的理解是预防急性中风进一步脑损伤的重要治疗靶点。这些见解可能为缺血性中风的创新治疗策略铺平道路。
