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星形胶质细胞连接蛋白-泛连接蛋白在急性脑损伤中的作用。

Role of astrocytes connexins - pannexins in acute brain injury.

作者信息

Tichauer Juan E, Rovegno Maximiliano

机构信息

Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Chile.

出版信息

Neurotherapeutics. 2025 Jan;22(1):e00523. doi: 10.1016/j.neurot.2025.e00523. Epub 2025 Jan 22.

Abstract

Acute brain injuries (ABIs) encompass a broad spectrum of primary injuries such as ischemia, hypoxia, trauma, and hemorrhage that converge into secondary injury where some mechanisms show common determinants. In this regard, astroglial connexin and pannexin channels have been shown to play an important role. These channels are transmembrane proteins sharing similar topology and form gateways between adjacent cells named gap junctions (GJs) and pores into unopposed membranes named hemichannels (HCs). In astrocytes, GJs and HCs enable intercellular communication and have active participation in normal brain physiological processes, such as calcium waves, synapsis modulation, regional blood flow regulation, and homeostatic control of the extracellular environment, among others. However, after acute brain injury, astrocytes can change their phenotype and modify the activity of both channels and hemichannels, which can result in the amplification of danger signals, increased mediators of inflammation, and neuronal death, contributing to the expansion of brain damage and neurological deterioration. This is known as secondary brain damage. In this review, we discussed the main biological mechanism of secondary brain damage with a particular focus on astroglial connexin and pannexin participation during acute brain injuries.

摘要

急性脑损伤(ABIs)包括一系列原发性损伤,如缺血、缺氧、创伤和出血,这些损伤会汇聚成继发性损伤,其中一些机制具有共同的决定因素。在这方面,星形胶质细胞连接蛋白和泛连接蛋白通道已被证明发挥重要作用。这些通道是跨膜蛋白,具有相似的拓扑结构,在相邻细胞之间形成名为缝隙连接(GJs)的通道,以及通向无对抗细胞膜的名为半通道(HCs)的孔道。在星形胶质细胞中,缝隙连接和半通道实现细胞间通讯,并积极参与正常脑生理过程,如钙波、突触调节、局部血流调节以及细胞外环境的稳态控制等。然而,急性脑损伤后,星形胶质细胞会改变其表型并改变通道和半通道的活性,这可能导致危险信号放大、炎症介质增加以及神经元死亡,从而导致脑损伤扩大和神经功能恶化。这被称为继发性脑损伤。在本综述中,我们讨论了继发性脑损伤的主要生物学机制,特别关注急性脑损伤期间星形胶质细胞连接蛋白和泛连接蛋白的参与情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7115/11840357/2fa3706abee7/gr1.jpg

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