A hydraulic resistance model for interstitial fluid flow in the brain.

Metabolic wastes may be cleared from the brain by the flow of interstitial fluid (ISF) through extracellular spaces in the parenchyma, as proposed in the glymphatic model. Owing to the difficulty of obtaining experimental measurements, fluid-dynamic models are employed to better understand parenchymal flow. Here we use an analytical solution for Darcy flow in a porous medium with line sources (representing penetrating arterioles) and line sinks (representing ascending venules) to model the flow and calculate the hydraulic resistance as a function of parenchymal permeability and ISF viscosity for various arrangements of the vessels. We calculate how the resistance varies with experimentally determined arrangements of arterioles and venules in mouse and primate brains. Based on experimental measurements of the relative numbers of arterioles and venules and their spacing, we propose idealized configurations for mouse and primate brains, consisting of regularly repeating patterns of arterioles and venules with even spacing. We explore how the number of vessels, vessel density, arteriole-to-venule ratio, and arteriole and venule distribution affect the hydraulic resistance. Quantifying how the geometry affects the resistance of brain parenchyma could help future modelling efforts characterize and predict brain waste clearance, with relevance to diseases such as Alzheimer's and Parkinson's.