Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke
Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke
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DOI：
10.1038/72256
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发表时间：
2000-02-01
期刊：
影响因子：
82.9
通讯作者：
Verkman, AS
中科院分区：
文献类型：
--
作者：
Manley, GT;Fujimura, M;Verkman, AS
脑水肿对许多常见神经系统疾病相关的发病率和死亡率有重大影响。然而，目前的治疗选择仅限于高渗剂和手术减压，这些疗法是70多年前引入的。在此我们表明，在急性水中毒引起的脑水肿模型中，水通道蛋白-4（AQP4）（一种神经胶质细胞膜水通道）缺陷的小鼠比野生型小鼠有更好的存活率。AQP4缺陷小鼠的脑组织含水量以及毛细血管周围星形胶质细胞足突的肿胀显著减少。在另一个脑水肿模型，即大脑中动脉闭塞导致的局灶性缺血性脑卒中中，AQP4缺陷小鼠的神经功能预后得到改善。以24小时大脑半球增大的百分比衡量，AQP4缺陷小鼠的脑水肿减少了35%。这些结果表明AQP4在调节脑水转运中起关键作用，并提示抑制AQP4可能为减少多种脑部疾病中的脑水肿提供一种新的治疗选择。
Cerebral edema contributes significantly to morbidity and death associated with many common neurological disorders. However, current treatment options are limited to hyperosmolar agents and surgical decompression, therapies introduced more than 70 years ago. Here we show that mice deficient in aquaporin-4 (AQP4), a glial membrane water channel, have much better survival than wild-type mice in a model of brain edema caused by acute water intoxication. Brain tissue water content and swelling of pericapillary astrocytic foot processes in AQP4-deficient mice were significantly reduced. In another model of brain edema, focal ischemic stroke produced by middle cerebral artery occlusion, AQP4-deficient mice had improved neurological outcome. Cerebral edema, as measured by percentage of hemispheric enlargement at 24 h, was decreased by 35% in AQP4-deficient mice. These results implicate a key role for AQP4 in modulating brain water transport, and suggest that AQP4 inhibition may provide a new therapeutic option for reducing brain edema in a wide variety of cerebral disorders.