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| Volume
69 Number 4 September 2002 |
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| Aquaporin Water Channels and Brain Edema | 242-248 |
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1Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco CA; and 2 Department of Infectious Diseases, St. George’s Hospital Medical School, London, UK.
* Present address: Department of Neurosurgery, Atkinson Morley’s Hospital, Copse Hill, London SW20 0NE UK.
Address all correspondence to Alan S. Verkman, M.D., Ph.D., Cardiovascular Research Institute, 1246 Health Sciences East Tower, Box 0521, University of California at San Francisco, San Francisco, CA 94143-0521.
Adapted from a presentation made to the Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York, NY by Dr. A. S. Verkman on December 1, 2000 and updated as of October 2001.
ABSTRACT
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.
KEYWORDS
Brain swelling, cytotoxic edema, vasogenic edema, water transport, water permeability, stroke, tumor, encephalopathy, transgenic mice.
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