Blood-brain Barrier: Structural Components and Function Under Physiologic and Pathologic Conditions
Blood-brain Barrier: Structural Components and Function Under Physiologic and Pathologic Conditions
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DOI：
10.1007/s11481-006-9025-3
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发表时间：
2006-09-01
影响因子：
6.2
通讯作者：
Kanmogne, Georgette D.
中科院分区：
文献类型：
--
作者：
Persidsky, Yuri;Ramirez, Servio H.;Kanmogne, Georgette D.
血脑屏障（BBB）是脑微血管内皮细胞（BMVEC）的专门系统，它保护大脑免受血液中有毒物质的影响，为脑组织提供营养，并将有害化合物从大脑过滤回血流。BMVEC与神经血管单位的其他组分（星形胶质细胞、周细胞、神经元和基底膜）之间的密切相互作用确保了中枢神经系统（CNS）的正常功能。通过物理（紧密连接）和代谢屏障（酶，不同的运输系统）严格限制通过BBB的运输。BMVEC的腔和近腔膜表面之间存在功能极性。由于受限的渗透性，BBB是将治疗剂递送到CNS中的限制因素。运输系统中的BBB破坏或改变在许多CNS疾病（HIV-1脑炎、阿尔茨海默病、缺血、肿瘤、多发性硬化和帕金森病）的发病机制中起重要作用。促炎物质和特定的疾病相关蛋白通常介导这种BBB功能障碍。尽管BBB功能障碍的潜在原因似乎多种多样，但共同的细胞内途径出现用于调节BBB结构和功能完整性。更好地了解紧密连接调节和影响运输系统的因素将允许开发治疗方法来改善健康和疾病中的BBB功能。
The blood-brain barrier (BBB) is the specialized system of brain microvascular endothelial cells (BMVEC) that shields the brain from toxic substances in the blood, supplies brain tissues with nutrients, and filters harmful compounds from the brain back to the bloodstream. The close interaction between BMVEC and other components of the neurovascular unit (astrocytes, pericytes, neurons, and basement membrane) ensures proper function of the central nervous system (CNS). Transport across the BBB is strictly limited through both physical (tight junctions) and metabolic barriers (enzymes, diverse transport systems). A functional polarity exists between the luminal and abluminal membrane surfaces of the BMVEC. As a result of restricted permeability, the BBB is a limiting factor for the delivery of therapeutic agents into the CNS. BBB breakdown or alterations in transport systems play an important role in the pathogenesis of many CNS diseases (HIV-1 encephalitis, Alzheimer's disease, ischemia, tumors, multiple sclerosis, and Parkinson's disease). Proinflammatory substances and specific disease-associated proteins often mediate such BBB dysfunction. Despite seemingly diverse underlying causes of BBB dysfunction, common intracellular pathways emerge for the regulation of the BBB structural and functional integrity. Better understanding of tight junction regulation and factors affecting transport systems will allow the development of therapeutics to improve the BBB function in health and disease.