The brain intercellular  communications,  transit  of  the  signaling  molecules,  neurotransmitters,   cytokines and substrates, the clearance of pathogenic metabolites, heat exchange are all linked to the  brain  water  metabolism. Many serious neurological conditions arise from or aggravated by the altered brain water metabolism (e.g. Alzheimer’s disease, idiopathic normal pressure hydrocephalus, migraine, traumatic brain injury and stroke, tumor migration).

According tothe commonly accepted orthodox theory, the nanodimentional brain interstitial space (ISS) presents a diffusion barrier admitting only the Fickian mass-transfer mechanism.  Contrary to the orthodox theory, in this research the  ISS  is  viewed  as  a  nanofluidic  domain  where fluid  flow   is governed by the slip-flow principles of nanofluidics. The water nanochannel aquaporin-4 of the astrocyte endfeet membranes ensures kinetic  control  over  water  movement  across  the  blood-brain  barrier while  the  pulsatory  intracranial  pressure  presents  the  driving  force  behind   the  transcapillary  water  flow.  A  novel  computational  model  of  brain  water  metabolism  has  been  developed  and  explored. The  model  demonstrates  good  predictability  in  respect  to  some  brain physiological  features,mass transfer of glucose, oxygen and carbon dioxide, and relevance tosome clinical conditions.

The new paradigm and the model may beemployed in neurobiological research, development of the AQP4-targeted drug therapy, optimization of the intrathecal drug delivery to the brain tumors, and in a research on a broad spectrum of water-metabolic-disorder-related conditions.

Keywords: Brain Nanofluidic Domain; Computational Model of Brain Water Metabolism; ConvectiveMassTransfer of Glucose, CO2 and O2; Implications for Nanomedicine.