Aquaporins: role in cerebral edema and brain water balance

Abstract

The regulation of water balance in the brain is crucial. A disruption in this equilibrium causes an increase in brain water content that significantly contributes to the pathophysiology of traumatic brain injury, hydrocephalus, and a variety of neurological disorders. The discovery of the aquaporin (AQP) family of membrane water channels has provided important new insights into the physiology and pathology of brain water homeostasis. A number of recent studies are described in the review that demonstrated the important role of AQP1 and AQP4 in brain water balance and cerebral edema. Phenotypic analyses of AQP deficient mice have allowed us to explore the role of these membrane water channels in the mechanisms of cytotoxic edema, vasogenic edema, and CSF production. These studies indicate that AQP4 plays significant role in the development of cytotoxic edema and the absorption of excess brain water resulting from vasogenic edema. They also have demonstrated the role of AQP1 in CSF production and maintenance of steady-state ICP. The ability to modulate water flux through AQP deletion has provided new insights into brain water homeostasis and suggested a number of new research directions. However, these efforts have not yet translated to the treatment human clinical diseases. These advances will require the development of AQP inhibitors and activators to establish the benefit modulating the function of these water channels.