Aquaporin water channels and brain edema.
Aquaporin water channels and brain edema.
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DOI：
10.1017/cbo9780511544910.012
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发表时间：
2002-09
期刊：
影响因子：
--
通讯作者：
M. Papadopoulos;Sanjeev Krishna;A. Verkman
中科院分区：
文献类型：
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作者：
M. Papadopoulos;Sanjeev Krishna;A. Verkman
脑水肿是常见神经系统疾病（如头部外伤、脑肿瘤、中风和肝功能衰竭）相关发病率和死亡率的主要原因。治疗选择仅限于甘露醇等渗透剂、手术减压和其他操作，这些都无法纠正导致脑肿胀的分子水平机制。最近的数据表明，水通道蛋白（AQP）输水蛋白可能为大脑中的水运动提供关键途径。 AQP1 在脉络丛中表达，可能促进脑脊液分泌。 AQP4 在毛细血管附近的星形胶质细胞足突和心室衬里的室管膜细胞中表达，这是细胞、血管和心室之间水运动的关键部位。在脑损伤和肿胀的实验模型中，AQP4 表达显着改变，缺乏 AQP4 的转基因小鼠在急性低钠血症和缺血性中风时可部分免受脑肿胀的影响。因此，水通道蛋白和脑水通道蛋白表达的调节剂是发现治疗脑肿胀的化合物的潜在目标。
Brain edema accounts for much of the morbidity and mortality associated with common neurological conditions such as head trauma, brain tumors, stroke and liver failure. Treatment options are limited to osmotic agents such as mannitol, surgical decompression, and other maneuvers, none of which correct the molecular-level mechanisms responsible for brain swelling. Recent data suggest that aquaporin (AQP) water-transporting proteins may provide a key route for water movement in the brain. AQP1 is expressed in choroid plexus and probably facilitates cerebrospinal fluid secretion. AQP4 is expressed in astrocyte foot processes near capillaries and in ependymal cells lining the ventricles -- key sites for water movement between the cellular, vascular, and ventricular compartments. AQP4 expression is markedly altered in experimental models of brain injury and swelling, and transgenic mice lacking AQP4 are partially protected from brain swelling in response to acute hyponatremia and ischemic stroke. Aquaporins and regulators of brain aquaporin expression are thus potential targets for discovery of compounds for treatment of brain swelling.