Nanofluidic Mechanism and Computational Model of the Brain Water Metabolism

Brain water metabolism is directly involved in the processes of cellular communication, transit of the signaling molecules, neurotransmitters, cytokines and substrates, participates in the clearance of pathogenic metabolites, etc. Many serious neurological conditions arise from the altered flow of the brain fluids (e.g. Alzheimer’s disease, idiopathic normal pressure hydrocephalus, migraine, traumatic brain injury and stroke, brain edema, etc.). 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 realistic mechanisms.

A novel computational model of brain water metabolism has been developed and explored. Based on an interdisciplinary approach, the brain interstitial space is viewed as a nanofluidic domain where fluid flow is 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 the brain water metabolism and relevance in explaining some 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 and in a research on a broad spectrum of water-metabolic-disorder-related conditions.