Role of aquaporin-4 in cerebral edema and stroke.
Cerebral edema plays a central role in the pathophysiology of many diseases of the central nervous system (CNS) including ischemia, trauma, tumors, inflammation, and metabolic disturbances. The formation of cerebral edema results in an increase in tissue water content and brain swelling which, if unchecked, can lead to elevated intracranial pressure (ICP), reduced cerebral blood flow, and ultimately cerebral herniation and death. Despite the clinical significance of cerebral edema, the mechanism of brain water transport and edema formation remain poorly understood. As a result, current therapeutic tools for managing cerebral edema have changed little in the past 90 years. "Malignant ischemic stroke" is characterized by high mortality (80%) and represents a major clinical problem in cerebrovascular disease. Widespread ischemic injury in these patients causes progressive cerebral edema, increased ICP, and rapid clinical decline. In response to these observations, a series of recent studies have begun to target cerebral edema in the management of large ischemic strokes. During cerebral edema formation, the glial water channel aquaporin-4 (AQP4) has been show to facilitate astrocyte swelling ("cytotoxic swelling"). AQP4 has also been seen to be responsible for the reabsorption of extracellular edema fluid ("vasogenic edema"). In the present review, the role of AQP4 in the development of cerebral edema is discussed with emphasis on its contribution to ischemic edema. We also examine the potential of AQP4 as a therapeutic target in edema associated with stroke.
Zador
Zsolt
Z
Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Room 101, San Francisco, CA 94110, USA.
Stiver
Shirley
S
Wang
Vincent
V
Manley
Geoffrey T
GT
D000818:Animals; D051401:Aquaporin 4 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D001929:Brain Edema / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D002490:Central Nervous System / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D014867:Water / Q000378:metabolism*; D014882:Water-Electrolyte Balance
C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D014867:Water