Dynamics of brain valves: putative rectification mechanisms for cerebrospinal fluid flow

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 bound the PVSs of penetrating arteries, separating them from brain extracellular space (ECS). Gaps between astrocyte endfeet provide a low-resistance pathway for fluid transport across the wall. Recent research suggests that the astrocyte endfeet may function as valves that rectify the CSF flow, leading to observed net flow in experiments. This study uses three-dimensional fluid-structure interaction (FSI) modeling to investigate the endfeet valve mechanism. Due to the unavailability of precise in vivo measurements for the shape and dimensions of the endfeet gaps, we explore potential asymmetric geometries in the endfeet: asymmetric gap and overlapping adjacent endfeet of different sizes. Our simulation results demonstrate flow rectification with high pumping efficiency. Additionally, we quantitatively study how net flow depends on parameters such as oscillatory pressure amplitude and frequency, gap size, and endfoot length ratio.