Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke

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 i ntroduced more than 70 years ago. Here we show that mice deficient in aquap orin-4 (AQP4), a glial membrane water channel, have much better survival th an wild-type mice in a model of brain edema caused by acute water intoxicat ion. Brain tissue water content and swelling of pericapillary astrocytic fo ot processes in AQP4-deficient mice were significantly reduced. In another model of brain edema, focal ischemic stroke produced by middle cerebral art ery occlusion, AQP4-deficient mice had improved neurological outcome. Cereb ral edema, as measured by percentage of hemispheric enlargement at 24 h, wa s decreased by 35% in AQP4-deficient mice. These results implicate a key ro le for AQP4 in modulating brain water transport, and suggest that AQP4 inhi bition may provide a new therapeutic option for reducing brain edema in a w ide variety of cerebral disorders.