Dynamics of brain valves: ostensible rectification mechanisms for cerebrospinal fluid flow.

Abstract

The flow of cerebrospinal fluid (CSF) through perivascular spaces (PVSs) is an important part of the brain's system for clearing metabolic waste. Astrocyte endfeet ensheath the PVSs of penetrating arteries, separating them from brain extracellular space (ECS). Gaps between astrocyte endfeet could provide a low-resistance pathway for fluid transport across the endfoot wall. Recent research suggests that the astrocyte endfeet may also function as valves that rectify the CSF flow, allowing oscillatory pressures to drive net flows like those observed in experiments. In this study, we employ fluid-structure interaction modelling to investigate the endfoot valve mechanism. Due to the unavailability of precise <i>in vivo</i> measurements of gap shape and size, we explore three possible, though idealized, geometric arrangements: wedge-shaped gaps, overlapping endfeet of different sizes and curvature of the endfoot wall. For each, we quantify the dependence of net flow on oscillatory pressure amplitude, frequency and other key parameters. For all three, our simulations demonstrate effective flow rectification at frequencies associated with functional hyperaemia, respiration and cardiac pulsation.