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The study gives an overview on the regulation of cerebral water content and of brain volume. The molecular mechanisms of the development and resolution of various oedema forms are discussed in detail. The physiological and pathophysiological role of the recently discovered molecular water channel proteins aquaporin-1 (AQP1) and aquaporin-4 (AQP4) as well as the importance of central neuroendocrine regulation by vasopressin and atriopeptin are reviewed based on the relevant literature and personal studies. Quantitative water maps based on the combination of multicompartment-T2, diffusion weighted MRI and T1 studies have proven to be powerful tools for studying new drugs against brain oedema brought about by various neuropathological conditions and for testing their efficacy both in animal experimental and clinical conditions. Non-peptide vasopressin antagonists, atriopeptin agonists and drugs targeting AQP4 are potential new families of oedema-decreasing drugs.

Regulation of tissue water content and brain volume is of critical importance for the normal functioning of the central nervous system (CNS), which, surrounded by the rigid cranium, is highly sensitive to any increase in the intracranial pressure. Alterations in cerebral water homeostasis and distribution may lead to neuronal and glial swelling known as cytotoxic brain edema, due to accumulation of intracellular water. Although numerous investigations have been performed to elucidate the underlying molecular basis and pathophysiology of brain edema, little is known about the regulation of water transport across the blood-brain barrier and between extra- and intracellular compartments of the brain parenchyma. The discovery and characterization of the aquaporin (AQP) family of membrane water channels provided molecular insight into fundamental processes of water transport across plasma membranes. Two AQPs are expressed abundantly in the mammalian brain: AQP1 in the apical plasma membranes of the cells of choroid plexus in the ventricles, where it has been suggested to participate in the secretion of cerebrospinal fluid and AQP4 in plasma membranes of ependymal cells and astrocytes. The role of AQP4 in the formation of brain oedema was suggested by some recent studies. These findings offer new potentials in brain oedema treatment.