中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (3): 632-645.doi: 10.4103/NRR.NRR-D-23-01336

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

缺血性脑卒中后反应性细胞极化的分子机制及应用

  

  • 出版日期:2025-03-15 发布日期:2024-06-25

Cell polarization in ischemic stroke: molecular mechanisms and advances

Yuanwei Li, Xiaoxiao Xu, Xuan Wu, Jiarui Li, Shiling Chen, Danyang Chen, Gaigai Li* , Zhouping Tang*   

  1. Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
  • Online:2025-03-15 Published:2024-06-25
  • Contact: Gaigai Li, MD, lgghuster@163.com; Zhouping Tang, MD, ddjtzp@163.com.
  • Supported by:
    The present work was supported by the National Natural Science Foundation of China, Nos. 82201474 (to GL), 82071330 (to ZT), and 92148206 (to ZT); Key Research and Discovery Program of Hubei Province, No. 2021BCA109 (to ZT).

摘要:

细胞极化指的是反应性细胞受到不同刺激后表现出双相功能的现象,最为经典的例子是巨噬细胞的M1/M2分型:M1型巨噬细胞能够分泌促炎因子,参与宿主防御,M2型巨噬细胞则能够抑制炎症反应,促进组织修复。后续的实验发现,这种促炎/抗炎的二元分类理论在小胶质细胞、星形胶质细胞和中性粒细胞中同样适用,并且广泛应用在各种病理环境下对细胞反应性改变的研究中。免疫反应和炎症应答在缺血性卒中病程进展中发挥着重要的作用。如果能够通过药物抑制具有促炎作用的1型细胞的产生,促进细胞向具有抗炎和神经保护作用的2型转化,或者调控1型细胞转为2型细胞,则有望减轻缺血性脑卒中后过度炎症反应带来的神经损伤,促进神经修复,从而改善患者预后。文章首先阐述缺血性脑卒中中小胶质细胞、星形胶质细胞和中性粒细胞极化现象的研究进展,然后总结目前已知的这三种细胞极化涉及的信号通路,如TLR4/NF-κB pathway、PPAR/RXR pathway和JAK/STAT pathway,并对细胞极化理论的意义和局限性进行了讨论。作者认为,利用分子药物调控细胞极化方向具有广阔的前景,通过探索病理状态下反应性细胞表型转变的分子机制,可能为缺血性脑卒中的治疗找到新的靶点。

https://orcid.org/0000-0002-4083-8145 (Gaigai Li); https://orcid.org/0000-0002-4153-8590 (Zhouping Tang)

Abstract: Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as ‘cell polarization.’ There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations (microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.

Key words: astrocyte polarization, immune regulation, inflammation, ischemic injury, microglia polarization, neutrophil polarization, signaling pathways, stroke