中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (4): 1359-1372.doi: 10.4103/NRR.NRR-D-24-01417

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

脑卒中不同阶段星形胶质细胞在血脑屏障中的作用

  

  • 出版日期:2026-04-15 发布日期:2025-07-25
  • 基金资助:
    国家自然科学基金项目(U21A20400,82104560,82104560)、北京市自然科学基金项目(7232279)、北京中医药大学项目(2024-JYBJJ,7232279);北京中医药大学项目(2024-JYBJBZD-043,2022-JYB-JBZR-004)。

Different roles of astrocytes in the blood–brain barrier during the acute and recovery phases of stroke

Jialin Cheng# , Yuxiao Zheng# , Fafeng Cheng# , Chunyu Wang, Jinhua Han, Haojia Zhang, Xin Lan, Chuxin Zhang, Xueqian Wang* , Qingguo Wang* , Changxiang Li*   

  1. College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
  • Online:2026-04-15 Published:2025-07-25
  • Contact: Changxiang Li, MD, changxiang1202@163.com; Xueqian Wang, MD, wxqbucm@126.com; Qingguo Wang, MD, wangqg8558@sina.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. U21A20400 (to QW); the Natural Science Foundation of Beijing, No. 7232279 (to XW); the National Natural Science Foundation of China, No. 82104560 (to CL); the Project of Beijing University of Chinese Medicine, Nos. 2024-JYBJBZD-043 (to CL), 2022-JYB-JBZR-004 (to XW).

摘要:

缺血性脑卒中是脑卒中的一种常见类型,是指脑部血流受阻,导致局部脑组织缺血、缺氧和坏死。缺血性脑卒中发生后,星形胶质细胞和血脑屏障都会发生形态和功能上的改变,但关于它们之间相互作用的讨论较少。这篇综述的目的是探讨缺血性脑卒中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。脑卒中后,内皮细胞和外周细胞的结构发生改变,导致血脑屏障的破坏,这种破坏使得各种促炎因子和趋化因子可以穿过血脑屏障。与此同时,星形胶质细胞膨胀并主要呈现出两种表型状态:A1 和 A2,它们在缺血性脑卒中的不同阶段表现出不同的作用。在急性期,A1 反应性星形胶质细胞分泌血管内皮生长因子(VEGF)、基质金属蛋白酶(MMP)、脂质载体蛋白2(LCN2)和其他细胞因子,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会产生五聚蛋白 3 (PTX3)、音速刺猬素 (Shh)、血管生成素-1 (Ang-1) 和其他保护内皮细胞的因子。此外,星形胶质细胞还通过铁死亡和外泌体间接影响血脑屏障的通透性。在缺血性脑卒中后期(恢复期),A1 和 A2 星形胶质细胞对胶质瘢痕的形成有不同的影响。A1 星形胶质细胞通过胶质纤维酸性蛋白(GAFP)、硫酸软骨素蛋白多糖(CSPG)、转化生长因子β(TGF-β)和其他因子促进胶质瘢痕形成并抑制轴突生长。与此相反,A2 星形胶质细胞通过血小板衍生生长因子(PDGF)和其他因子促进轴突生长,在血管重塑中发挥着至关重要的作用。因此,加强对星形胶质细胞和血脑屏障之间的病理变化和相互作用的了解,是防止急性脑卒中进一步脑损伤的重要治疗目标,这一认识可能为缺血性脑卒中的创新治疗策略铺平道路。

https://orcid.org/0000-0001-8382-1717 (Changxiang Li); https://orcid.org/0000-0002-7682-3877 (Xueqian Wang); https://orcid.org/0000-0003-2752-1925 (Qingguo Wang)

关键词:

Abstract: 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.

Key words: astrocytes, axon, blood–brain barrier, cytokines, endothelial cells, glial scar, ischemic stroke, phenotype, remodel, vascular