Role of aquaporin-4 in cerebral edema and stroke.
Role of aquaporin-4 in cerebral edema and stroke.
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DOI：
10.1007/978-3-540-79885-9_7
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发表时间：
2009
影响因子：
--
通讯作者：
Manley, Geoffrey T
中科院分区：
文献类型：
--
作者：
Zador, Zsolt;Stiver, Shirley;Wang, Vincent;Manley, Geoffrey T
脑水肿在许多中枢神经系统(CNS)疾病的病理生理学中起着核心作用，包括缺血、创伤、肿瘤、炎症和代谢紊乱。脑水肿的形成会导致组织含水量增加和脑肿胀，如果不加以控制，可能会导致颅内压升高，脑血流量减少，最终导致脑突出和死亡。尽管脑水肿具有临床意义，但脑水转运和脑水肿形成的机制仍然知之甚少。因此，在过去的90年里，目前用于管理脑水肿的治疗工具几乎没有变化。“恶性缺血性卒中”的特点是死亡率高(约80%)，是脑血管疾病的主要临床问题。在这些患者中，广泛的缺血性损伤会导致进行性脑水肿，增加颅内压，并导致临床迅速下降。作为对这些观察结果的回应，最近的一系列研究已经开始针对大面积缺血性中风的治疗中的脑水肿。在脑水肿形成过程中，胶质水通道蛋白-4(AQP4)促进星形胶质细胞肿胀(“细胞毒性肿胀”)。AQP4也被认为与细胞外水肿液的重吸收(“血管源性水肿症”)有关。本文就AQP4在脑水肿发生发展中的作用作一综述，重点介绍其在缺血性脑水肿中的作用。我们还研究了AQP4作为卒中相关水肿的治疗靶点的潜力。
Cerebral edema plays a central role in the pathophysiology of many diseases of the central nervous system (CNS) including ischemia, trauma, tumors, inflammation, and metabolic disturbances. The formation of cerebral edema results in an increase in tissue water content and brain swelling which, if unchecked, can lead to elevated intracranial pressure (ICP), reduced cerebral blood flow, and ultimately cerebral herniation and death. Despite the clinical significance of cerebral edema, the mechanism of brain water transport and edema formation remain poorly understood. As a result, current therapeutic tools for managing cerebral edema have changed little in the past 90 years. “Malignant ischemic stroke” is characterized by high mortality (~80%) and represents a major clinical problem in cerebrovascular disease. Widespread ischemic injury in these patients causes progressive cerebral edema, increased ICP, and rapid clinical decline. In response to these observations, a series of recent studies have begun to target cerebral edema in the management of large ischemic strokes. During cerebral edema formation, the glial water channel aquaporin-4 (AQP4) has been show to facilitate astrocyte swelling (“cytotoxic swelling”). AQP4 has also been seen to be responsible for the reabsorption of extracellular edema fluid (“vasogenic edema”). In the present review, the role of AQP4 in the development of cerebral edema is discussed with emphasis on its contribution to ischemic edema. We also examine the potential of AQP4 as a therapeutic target in edema associated with stroke.