突破屏障:促炎细胞因子在血脑屏障功能障碍中的作用

Breaking the Barrier: The Role of Proinflammatory Cytokines in BBB Dysfunction.

作者信息

Gryka-Marton Małgorzata, Grabowska Anna D, Szukiewicz Dariusz

机构信息

Laboratory of the Blood-Brain Barrier, Department of Biophysics, Physiology & Pathophysiology, Faculty of Health Sciences, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland.

出版信息

Int J Mol Sci. 2025 Apr 9;26(8):3532. doi: 10.3390/ijms26083532.

Abstract

The BBB is created by a special system of brain microvascular endothelial cells (BMECs), pericytes (PCs), the capillary basement membrane, and the terminal branches ("end-feet") of astrocytes (ACs). The key function of the BBB is to protect the central nervous system (CNS) from potentially harmful/toxic substances in the bloodstream by selectively controlling the entry of cells and molecules, including nutrients and components of the immune system. The loss of BBB integrity in response to neuroinflammation, as manifested by an increase in permeability, depends predominantly on the activity of proinflammatory cytokines. However, the pathomechanism of structural and functional changes in the BBB under the influence of individual cytokines is still poorly understood. This review summarizes the current state of knowledge on this topic, which is important from both pathophysiological and therapeutic points of view. The structures and functions of all components of the BBB are reviewed, with emphasis given to differences between this and other locations of the circulatory system. The protein composition of the interendothelial tight junctions in the context of regulating BBB permeability is presented, as is the role of pericyte-BMEC interactions in the exchange of metabolites, ions, and nucleic acids. Finally, the documented actions of proinflammatory cytokines within the BBB are discussed.

摘要

血脑屏障由脑微血管内皮细胞(BMECs)、周细胞(PCs)、毛细血管基底膜以及星形胶质细胞(ACs)的终末分支(“终足”)组成的特殊系统构成。血脑屏障的关键功能是通过选择性地控制细胞和分子(包括营养物质和免疫系统成分)的进入,保护中枢神经系统(CNS)免受血流中潜在有害/有毒物质的侵害。血脑屏障完整性因神经炎症而丧失,表现为通透性增加,这主要取决于促炎细胞因子的活性。然而,在单个细胞因子影响下血脑屏障结构和功能变化的发病机制仍知之甚少。本综述总结了该主题的当前知识状态,这从病理生理和治疗角度来看都很重要。对血脑屏障所有组成部分的结构和功能进行了综述,重点强调了其与循环系统其他部位的差异。介绍了在内皮细胞间紧密连接调节血脑屏障通透性背景下的蛋白质组成,以及周细胞与脑微血管内皮细胞相互作用在代谢物、离子和核酸交换中的作用。最后,讨论了促炎细胞因子在血脑屏障内已被证实的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fd0/12026921/c64a2066da52/ijms-26-03532-g001.jpg

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