Gaps in the wall of a perivascular space act as valves to produce a directed flow of cerebrospinal fluid: a hoop-stress model

Abstract

The flow of cerebrospinal fluid (CSF) along 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. Gaps between astrocyte endfeet might provide a low-resistance pathway for fluid transport across the wall. Recent studies suggest that the astrocyte endfeet function as valves that rectify the CSF flow, producing the net flow observed in pial PVSs by changing the size of the gaps in response to pressure changes. In this study, we quantify this rectification based on three features of the PVSs: the quasi-circular geometry, the deformable endfoot wall, and the pressure oscillation inside. We provide an analytical model, based on the thin-shell hoop-stress approximation, and predict a pumping efficiency of about 0.4, which would contribute significantly to the observed flow. When we add the flow resistance of the extracellular space (ECS) to the model, we find an increased net flow during sleep, due to the known increase in ECS porosity (decreased flow resistance) compared to that in the awake state. We corroborate our analytical model with three-dimensional fluid–solid interaction simulations.