title: A computational model of cerebrospinal fluid production and reabsorption driven by Starling forces.
abstract: Experimental evidence has cast doubt on the classical model of river-like cerebrospinal fluid (CSF) flow from the choroid plexus to the arachnoid granulations. We propose a novel model of water transport through the parenchyma from the microcirculation as driven by Starling forces. This model investigates the effect of osmotic pressure on water transport between the cerebral vasculature, the extracellular space (ECS), the perivascular space (PVS), and the CSF. A rigorous literature search was conducted focusing on experiments which alter the osmolarity of blood or ventricles and measure the rate of CSF production. Investigations into the effect of osmotic pressure on the volume of ventricles and the flux of ions in the blood, choroid plexus epithelium, and CSF are reviewed. Increasing the osmolarity of the serum via a bolus injection completely inhibits nascent fluid flow production in the ventricles. A continuous injection of a hyperosmolar solution into the ventricles can increase the volume of the ventricle by up to 125%. CSF production is altered by 0.231 μL per mOsm in the ventricle and by 0.835 μL per mOsm in the serum. Water flux from the ECS to the CSF is identified as a key feature of intracranial dynamics. A complete mathematical model with all equations and scenarios is fully described, as well as a guide to constructing a computational model of intracranial water balance dynamics. The model proposed in this article predicts the effects the osmolarity of ECS, blood, and CSF on water flux in the brain, establishing a link between osmotic imbalances and pathological conditions such as hydrocephalus and edema.
authors.forename: Joel
authors.initials: J
authors.lastname: Buishas
authors.forename: Ian G
authors.initials: IG
authors.lastname: Gould
authors.affiliation: Andreas A. Linninger, Professor of Chemical Engineering and Bioengineering, University of Illinois at Chicago, Laboratory for Product and Process Design, M/C 063, 851 S. Morgan St. - 218 SEO, Chicago, Illinois 60607-7000, linninge@uic.edu.
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Linninger
mesh_terms: D000328:Adult; D000818:Animals; D001692:Biological Transport; D001834:Body Water / Q000502:physiology*; D002552:Cerebral Ventricles / Q000378:metabolism*; D002555:Cerebrospinal Fluid / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D003198:Computer Simulation; D006801:Humans; D009994:Osmolar Concentration; D009997:Osmotic Pressure