Aquaporins 4 are channels in the astrocyte membrane that regulate the extracellular osmotic pressure; in other words, they control the water balance of the brain. Therefore, they are channels for the transport of water. However, aquaporins were first described in the kidney tubular system where they were shown to increase sharply the capacity for water passage. In the brain, they are most abundant in the glial (neuroglial) processes and they are called aquaporins 4 (AQP4) and they are in close contact with capillaries and the CSF. AQP1, on the other hand, is present in epithelial cells of the choroid plexus.
Aquaporin 4 is located in the astrocyte membrane and it is concentrated in large number in the end-feet region close to capillaries and in astrocyte processes close to the CSF (cerebro-spinal fluid). The main function of AQP4 in the normal brain is to transport water. In vasogenic brain edema, when water accumulates extracellularly, AQP4 contributes to the removal of excess water. This kind of edema happens when capillaries become leaky through traumatic brain injury. However, during cerebral ischemia (stroke) and hypoxia (which happens to high-altitude mountain climbers), water accumulates intracellularly as the presence of AQP4 seems to increase the intracellular edema by allowing more water to enter the astrocyte. Such cytotoxic brain edema is caused by failure of energy-dependent ion pumping.
Brain edema is a serious and often life-threatening medical condition. Therefore, the discovery of the relationship between aquaporins and brain edema led to an intensive scientific research to look for drugs that can alter and control the activity of aquaporins. In animal experiments, inhibitors of AQP4 can reduce cytotoxic edema caused by hypoxia, whereas they seem to worsen vasogenic edema caused by traumatic injury.