Zador Zsolt, Stiver Shirley, Wang Vincent, Manley Geoffrey T
Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Room 101, San Francisco, CA 94110, USA.
Handb Exp Pharmacol. 2009(190):159-70. doi: 10.1007/978-3-540-79885-9_7.
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.
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，这些疾病包括缺血、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（ICP）升高、脑血流量减少，最终导致脑疝和死亡。尽管脑水肿具有临床重要性，但其脑水转运和水肿形成机制仍知之甚少。因此，在过去90年里，目前用于治疗脑水肿的工具几乎没有变化。“恶性缺血性中风”的特点是高死亡率（80%），是脑血管疾病中的一个主要临床问题。这些患者广泛的缺血性损伤会导致进行性脑水肿、ICP升高和临床快速恶化。针对这些观察结果，最近一系列研究已开始将脑水肿作为大面积缺血性中风治疗的靶点。在脑水肿形成过程中，胶质水通道水通道蛋白4（AQP4）已被证明可促进星形胶质细胞肿胀（“细胞毒性肿胀”）。AQP4也被认为负责细胞外水肿液的重吸收（“血管源性水肿”）。在本综述中，将讨论AQP4在脑水肿发展中的作用，重点是其对缺血性水肿的贡献。我们还将研究AQP4作为中风相关水肿治疗靶点的潜力。
