Blood-brain barrier Na transporters in ischemic stroke.
Blood-brain barrier Na transporters in ischemic stroke.
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DOI：
10.1016/bs.apha.2014.06.011
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发表时间：
2014-01-01
期刊：
影响因子：
--
通讯作者：
O'Donnell, Martha E
中科院分区：
文献类型：
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作者：
O'Donnell, Martha E
血脑屏障（BBB）内皮细胞形成高度限制溶质在血液和脑之间通过的屏障。已经描述了许多BBB转运机制，其介导溶质穿过屏障进入或离开脑的跨细胞运动。一个经常被忽视的BBB转运蛋白是离子转运蛋白。血脑屏障有丰富的离子转运蛋白和通道，携带Na、K、Cl、HCO 3、Ca和其他离子。其中许多不对称地分布在腔和近腔膜之间，使BBB内皮细胞能够执行离子穿过血液和脑之间的屏障的矢量运输。以这种方式，BBB执行调节脑间质液的体积和组成的重要功能。通过腔和近腔转运蛋白和通道的功能性偶联，BBB将Na、Cl和其他离子从血液运送到脑中，在健康脑中产生高达30%的脑间质液。在缺血性中风期间，脑水肿通过涉及BBB管腔Na转运体活性增加的过程形成，导致Na、Cl和水“过度分泌”到脑组织中。本文综述了血脑屏障钠转运体在脑卒中水肿形成中的作用，重点是钠-钾-氯共转运和钠/氢交换。证据表明，这些转运蛋白提供有效的治疗目标，减少中风中的水肿也进行了讨论，是最近的研究结果有关的信号通路负责缺血刺激的血脑屏障钠转运蛋白。
Blood-brain barrier (BBB) endothelial cells form a barrier that is highly restrictive to passage of solutes between blood and brain. Many BBB transport mechanisms have been described that mediate transcellular movement of solutes across the barrier either into or out of the brain. One class of BBB transporters that is all too often overlooked is that of the ion transporters. The BBB has a rich array of ion transporters and channels that carry Na, K, Cl, HCO3, Ca, and other ions. Many of these are asymmetrically distributed between the luminal and abluminal membranes, giving BBB endothelial cells the ability to perform vectorial transport of ions across the barrier between blood and brain. In this manner, the BBB performs the important function of regulating the volume and composition of brain interstitial fluid. Through functional coupling of luminal and abluminal transporters and channels, the BBB carries Na, Cl, and other ions from blood into brain, producing up to 30% of brain interstitial fluid in healthy brain. During ischemic stroke cerebral edema forms by processes involving increased activity of BBB luminal Na transporters, resulting in "hypersecretion" of Na, Cl, and water into the brain interstitium. This review discusses the roles of luminal BBB Na transporters in edema formation in stroke, with an emphasis on Na-K-Cl cotransport and Na/H exchange. Evidence that these transporters provide effective therapeutic targets for reduction of edema in stroke is also discussed, as are recent findings regarding signaling pathways responsible for ischemia stimulation of the BBB Na transporters.