Novel Computational Model of the Brain Water Metabolism: Introducing an Interdisciplinary Approach

Brain water metabolism ensures the processes of cellular communication, transit of the signaling molecules, neurotransmitters, cytokines and substrates, participates in the clearance of pathogenic metabolites. Many neurological conditions that present serious clinical problems arise from altered fluid flow (e.g. Alzheimer’s disease, idiopathic normal pressure hydrocephalus, migraine, traumatic brain injury and stroke). At present, the orthodox theory fails to explain the accumulated experimental evidence and clinical data on the brain water metabolism. Modeling becomes an important approach to testing current theories and developing new working mechanisms. A novel computational model of brain water metabolism has been developed and explored. Using an interdisciplinary approach the long-recognized nanodimentionality of the brain interstitial space is now viewed as a nanofluidic domain with the fluid flow there governed by the slip-flow principles of nanofluidics. Aquaporin-4 (AQP4) of the astrocyte endfeet membranes ensures kinetic control over water movement across the blood-brain barrier. The pulsatory intracranial pressure presents the driving force behind the transcapillary water flow. The model demonstrates good predictability in respect to some physiological features of brain water metabolism and relevance in explaining clinical conditions. The model may find its use in neurobiological research, development of the AQP4-targeted drug therapy, optimization of the intrathecal drug delivery to the brain tumours, in a research on a broad spectrum of water-metabolic-disorder-related conditions.