Blood-Brain Barrier Damage in Ischemic Stroke and Its Regulation by Endothelial Mechanotransduction.
Blood-Brain Barrier Damage in Ischemic Stroke and Its Regulation by Endothelial Mechanotransduction.
复制标题
缺血性中风中的血脑屏障损伤及其内皮机械传导的调节。
DOI：
10.3389/fphys.2020.605398
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发表时间：
2020
影响因子：
4
通讯作者：
Ebong EE
中科院分区：
文献类型：
--
作者：
Nian K;Harding IC;Herman IM;Ebong EE
在美国，缺血性中风是导致死亡的主要原因之一，通常会导致血脑屏障(BBB)的破坏。血脑屏障及其支持细胞统称为“神经血管单位”，是大脑的多细胞微血管系统，双向调节血液、离子、氧气和细胞从循环进入大脑的运输。因此，它对维持中枢神经系统的动态平衡至关重要。血脑屏障破坏与紧密连接蛋白和血脑屏障转运体的表达改变有关，被认为加重了缺血性卒中引起的脑损伤，限制了目前临床治疗的潜力，如重组组织型纤溶酶原激活剂。越来越多的证据表明，内皮机械生物学，即将机械力转化为生化信号，有助于调节周围血管系统的功能，并可能类似地维持血脑屏障的完整性。例如，内皮细胞糖基化蛋白(GCX)是一种延伸到血管管腔的糖蛋白-蛋白多糖，在血脑屏障的内皮细胞上大量表达，并已被证明调节血脑屏障的通透性。在这篇综述中，我们将着重于我们对缺血性卒中后血脑屏障损伤的机制的理解，强调目前和未来潜在的用于血脑屏障保护和恢复的新的药理学策略。最后，我们将解决目前关于内皮细胞机械转导在血脑屏障维持中的知识，特别是专注于内皮细胞GCX的潜在作用。
Ischemic stroke, a major cause of mortality in the United States, often contributes to disruption of the blood-brain barrier (BBB). The BBB along with its supportive cells, collectively referred to as the “neurovascular unit,” is the brain’s multicellular microvasculature that bi-directionally regulates the transport of blood, ions, oxygen, and cells from the circulation into the brain. It is thus vital for the maintenance of central nervous system homeostasis. BBB disruption, which is associated with the altered expression of tight junction proteins and BBB transporters, is believed to exacerbate brain injury caused by ischemic stroke and limits the therapeutic potential of current clinical therapies, such as recombinant tissue plasminogen activator. Accumulating evidence suggests that endothelial mechanobiology, the conversion of mechanical forces into biochemical signals, helps regulate function of the peripheral vasculature and may similarly maintain BBB integrity. For example, the endothelial glycocalyx (GCX), a glycoprotein-proteoglycan layer extending into the lumen of bloods vessel, is abundantly expressed on endothelial cells of the BBB and has been shown to regulate BBB permeability. In this review, we will focus on our understanding of the mechanisms underlying BBB damage after ischemic stroke, highlighting current and potential future novel pharmacological strategies for BBB protection and recovery. Finally, we will address the current knowledge of endothelial mechanotransduction in BBB maintenance, specifically focusing on a potential role of the endothelial GCX.
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影响因子：
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