AQP-4 is the major membrane water channel in the central nervous system. The channel is expressed in astrocyte foot processes in direct contact with capillary vessels in the brain suggesting a role in water transport under normal and pathological conditions. Indeed, transgenic mice lacking AQP-4 have reduced brain swelling and improved neurological outcome following water intoxication and focal cerebral ischemia. In contrast, brain swelling and clinical outcome are worse in AQP-4-null mice in models of vasogenic (fluid leak) edema caused by freeze-injury and brain tumor, probably due to impaired AQP-4-dependent brain water clearance.nIn addition, it has been recently shown that neuromyelitis optica (NMO), an inflammatory demyelinating disease that selectively affects optic nerves and spinal cord, is caused by the development of an autoantibody directed against AQP-4