Wei Chao, Jiang Wei, Luo Minmin, Shao Feng
State Key Laboratory of Cognitive Science and Mental Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing, PR China.
National Institute of Biological Sciences, Beijing, PR China.
Trends Cell Biol. 2025 Mar 25. doi: 10.1016/j.tcb.2025.02.012.
The blood-brain barrier, recently reintroduced as the blood-brain border (BBB), is a dynamic interface between the central nervous system (CNS) and the bloodstream. Disruption of the BBB exposes the CNS to peripheral pathogens and harmful substances, causing or worsening various CNS diseases. While traditional views attribute BBB failure to tight junction disruption or increased transcytosis, recent studies highlight the critical role of gasdermin D (GSDMD) pore formation in brain endothelial cells (bECs) during BBB disruption by lipopolysaccharide (LPS) or bacterial infections. This mechanism may also be involved in neurological complications like the 'brain fog' seen in long COVID. Pore formation in bECs may represent a prevalent mechanism causing BBB leakage. Investigating membrane-permeabilizing pores or channels and their effects on BBB integrity is a growing area of research. Further exploration of molecular processes that maintain, disrupt, and restore bEC membrane integrity will advance our understanding of brain vasculature and aid in developing new therapies for BBB-related diseases.
血脑屏障，最近重新定义为血脑边界（BBB），是中枢神经系统（CNS）与血流之间的动态界面。血脑屏障的破坏会使中枢神经系统暴露于外周病原体和有害物质中，从而引发或加重各种中枢神经系统疾病。虽然传统观点认为血脑屏障功能障碍是由于紧密连接破坏或转胞吞作用增加，但最近的研究强调了在脂多糖（LPS）或细菌感染导致血脑屏障破坏期间，gasdermin D（GSDMD）在脑内皮细胞（bECs）中形成孔道的关键作用。这种机制也可能与诸如长期新冠中出现的“脑雾”等神经并发症有关。脑内皮细胞中的孔道形成可能是导致血脑屏障渗漏的普遍机制。研究膜通透性孔道或通道及其对血脑屏障完整性的影响是一个不断发展的研究领域。进一步探索维持、破坏和恢复脑内皮细胞膜完整性的分子过程，将增进我们对脑血管系统的理解，并有助于开发针对血脑屏障相关疾病的新疗法。
