Ronaldson Patrick T, Davis Thomas P
Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, USA.
Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, USA.
Brain Res. 2015 Oct 14;1623:39-52. doi: 10.1016/j.brainres.2015.03.018. Epub 2015 Mar 18.
The blood-brain barrier (BBB) is a physical and biochemical barrier that precisely regulates the ability of endogenous and exogenous substances to accumulate within brain tissue. It possesses structural and biochemical features (i.e., tight junction and adherens junction protein complexes, influx and efflux transporters) that work in concert to control solute permeation. Oxidative stress, a critical component of several diseases including cerebral hypoxia/ischemia and peripheral inflammatory pain, can cause considerable injury to the BBB and lead to significant CNS pathology. This suggests a critical need for novel therapeutic approaches that can protect the BBB in diseases with an oxidative stress component. Recent studies have identified molecular targets (i.e., putative membrane transporters, intracellular signaling systems) that can be exploited for optimization of endothelial drug delivery or for control of transport of endogenous substrates such as the antioxidant glutathione (GSH). In particular, targeting transporters offers a unique approach to protect BBB integrity by promoting repair of cell-cell interactions at the level of the brain microvascular endothelium. This review summarizes current knowledge in this area and emphasizes those targets that present considerable opportunity for providing BBB protection and/or promoting BBB repair in the setting of oxidative stress. This article is part of a Special Issue entitled SI: Cell Interactions In Stroke.
血脑屏障（BBB）是一种物理和生化屏障，它精确地调节内源性和外源性物质在脑组织中积累的能力。它具有结构和生化特征（即紧密连接和黏附连接蛋白复合物、流入和流出转运体），这些特征协同作用以控制溶质渗透。氧化应激是包括脑缺氧/缺血和外周炎性疼痛在内的几种疾病的关键组成部分，可对血脑屏障造成相当大的损伤并导致严重的中枢神经系统病理学改变。这表明迫切需要新的治疗方法，以在具有氧化应激成分的疾病中保护血脑屏障。最近的研究已经确定了分子靶点（即假定的膜转运体、细胞内信号系统），可利用这些靶点来优化内皮细胞药物递送或控制内源性底物如抗氧化剂谷胱甘肽（GSH）的转运。特别是，靶向转运体提供了一种独特的方法，通过促进脑微血管内皮水平的细胞间相互作用修复来保护血脑屏障的完整性。本综述总结了该领域的当前知识，并强调了那些在氧化应激情况下为提供血脑屏障保护和/或促进血脑屏障修复提供了相当大机会的靶点。本文是名为“SI：中风中的细胞相互作用”的特刊的一部分。
