TPA and proteolysis in the neurovascular unit
TPA and proteolysis in the neurovascular unit
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DOI：
10.1161/01.str.0000115164.80010.8a
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发表时间：
2004-02-01
期刊：
影响因子：
8.3
通讯作者：
Moskowitz, MA
中科院分区：
文献类型：
--
作者：
Lo, EH;Broderick, JP;Moskowitz, MA
NINDS卒中进展审查小组提出的主要建议之一是将重点从单纯以神经为中心的细胞死亡观点转向更综合的方法，即在脑缺血期间考虑所有脑细胞和基质的反应（见图）。神经血管单位的概念（主要包括内皮、星形胶质细胞和神经元）提供了一个模块化的框架，其中细胞-细胞信号传导和细胞-基质相互作用介导了整个组织对中风及其治疗的反应。毫无疑问，如果及时进行血管再灌注，就像缺血心肌一样，在机械上或药理学上可以防止细胞死亡并挽救大脑。然而，在某些情况下，溶栓和再灌注导致脑出血和水肿。在这里，我们研究了组织纤溶酶原激活剂（tPA）卒中治疗后的有益和潜在有害结果可能部分与神经血管单位内基质蛋白水解有关的假设，并回顾了该领域的最新进展。
One of the major recommendations emerging from the NINDS Stroke Progress Review Group was to shift the emphasis from a purely neurocentric view of cell death toward a more integrative approach whereby responses in all brain cells and matrix are considered during cerebral ischemia (see Figure). The concept of the neurovascular unit (fundamentally comprising endothelium, astrocyte, and neuron) provides a modular framework where cell-cell signaling and cell-matrix interactions mediate the overall tissue response to stroke and its treatments. 1 There is no doubt that reperfusing blood vessels mechanically or pharmacologically prevents cell death and rescues brain when performed in a timely manner, as it does in ischemic myocardium. However, under some circumstances, thrombolysis and reperfusion lead to cerebral hemorrhage and edema. Here, we examine the hypothesis that beneficial versus potentially deleterious outcomes after tissue plasminogen activator (tPA) stroke therapy may relate in part to matrix proteolysis within the neurovascular unit, and review recent advances in this area.