Abstract
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.
Highlights
The brain interstitial and the cerebrospinal fluids are involved in the nutrient and gas transport, non-synaptic intercellular communication, signal transduction, transport and targeted delivery of drugs and metabolites, ionic homeostasis, formation and resolution of the brain β-amyloid deposits, the migration of cells, transfer of heat generated by neuractivity [1,2].Developed over a century ago the classic concept of the cerebrospinal fluid (CSF) movement asserts that the choroid plexus is an exclusive site of the CSF secretion with the fluid flowing on to the subarachnoid space to sink in the sagittal sinus [3]
It is clearly understood at present that the knowledge of fluid/water dynamics in the brain interstitial space together with that of neural circuits is the way to clarify the complex physiology of the brain [1]
An adopted interdisciplinary approach has made it possible to consider the brain interstitial space as a nanofluidic domain where water movement is governed by the slip-flow principles of nanofluidics
Summary
Developed over a century ago the classic concept of the cerebrospinal fluid (CSF) movement asserts that the choroid plexus is an exclusive site of the CSF secretion with the fluid flowing on to the subarachnoid space to sink in the sagittal sinus [3]. Filtration and reabsorption of water at the microvessel level involves all the perivascular, the interstitial and the subarachnoid spaces. The volumetric exchange rate of water may vary from 0.35 to 520 ml/min [11]. The flow of this magnitude presents a problem for any potential water metabolism mechanism that would have to account for it
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