Computational modelling of fluid and solute transport in the brain

The glymphatic system is proposed to be a unidirectional fluid and solute circulation pathway in the brain involving transport through perivascular spaces, brain interstitium and glial cells. Some aspects of the glymphatic hypothesis are controversial, particularly the outflow pathway, and little is known about the forces that govern such fluid transport at each stage. Computational and mathematical modelling approaches can be valuable for testing hypotheses and are a useful adjunct to experimental research in this field. This article presents an overview of computational modelling studies associated with glymphatic fluid transport in the brain, from fluid inflow, transparenchymal transport and outflow. A broad range of modelling approaches have been used to investigate fluid and solute transport from purely analytical models to hydraulic resistance networks and computational fluid dynamics models. Most of the modelling attention has focused on periarterial inflow and transport through the parenchyma. Collectively these studies suggest that arterial pulsation is unlikely to be the sole inflow driving force, and diffusion is most likely the dominant mode of transport in the parenchymal extracellular spaces. Models of efflux are limited and have not been able to shed light on the driving forces for fluid outflow from the central nervous system.