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

Geoffrey T. Manley, Miki Fujimura, Tonghui Ma, Nobuo Noshita, Ferda Filiz, Andrew W. Bollen, Pak Chan, A. S. Verkman

Research output: Contribution to journalArticlepeer-review

1195 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)159-163
Number of pages5
JournalNature Medicine
Volume6
Issue number2
DOIs
Publication statusPublished - 2000 Feb

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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