Aquaporins pp 159-170 | Cite as

Role of Aquaporin-4 in Cerebral Edema and Stroke

  • Zsolt Zador
  • Shirley Stiver
  • Vincent Wang
  • Geoffrey T. Manley
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 190)

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 cerebrovascu-lar 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 reabsorp-tion 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.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Zsolt Zador
    • 1
  • Shirley Stiver
    • 1
  • Vincent Wang
    • 1
  • Geoffrey T. Manley
    • 1
  1. 1.Department of Neurological SurgeryUniversity of California, San FranciscoSan FranciscoUSA

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