Water diffusion across lipid bilayers is slow and mainly depends on osmotic forces. In biological membranes, aquaporins (AQPs), facilitate the bi-directional water transport through the lipid bilayer. AQP-4 is the most widely expressed AQP in the brain and is present on astrocyte end-feet surrounding capillaries or lining the pia and ventricles. Neither oligodendrocytes nor neurons express AQP-4, but microglia can be stimulated to synthetize the water channel. There are two isoforms of the AQP-4 protein, called M1 and M23. The expression ratio of these determines the assembly in orthogonal arrays of particles and the functionality of the waterchannels. In vitro, AQP-4 expression can be influenced through the addition of solutes or changes in culture conditions. During pathology, AQP-4 is upregulated in vasogenic brain edema typically found in or around tumors. Cytotoxic edema is encountered during acute hyponatraemia or ischemia/reperfusion and is frequently accompanied by upregulation of AQP-4. This might contribute to early cytotoxic edema formation but also facilitate the clearance of extracellular water during the later phases of edema. After traumatic brain injury, AQP-4 is downregulated in the contusion core, but slightly upregulated in the pericontusional areas. Drug-induced upregulation or reinstitution of perivascular location of AQP-4 after traumatic brain injury by eg., sulphoraphane or magnesium, attenuates post-traumatic brain swelling. During neuromyelitis optica, antibodies against AQP-4 are found in sera and seem to be responsible for eliciting the disease. AQP-4 forms an interesting target for drug discovery to improve the outcome of patients who suffer from brain edema.
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