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May 8th, 2025
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Simula Research Laboratory
neuroscience
biorxiv

Stretch and flow at the gliovascular interface: high-fidelity modelling of the mechanics of astrocyte endfeet

Causemann, M.Open in Google Scholar•Enger, R.Open in Google Scholar•Rognes, M. E.Open in Google Scholar

Astrocyte endfeet form a near-continuous sheath around the brain's vasculature, defining the perivascular space (PVS) implicated in fluid flow and solute transport. Yet, their precise physiological role remains incompletely understood. This study combines electron microscopy data with a high-fidelity poroelastic computational model to investigate the mechanical interplay at the gliovascular interface. We simulated tissue displacement and fluid flow within detailed reconstructions of the PVS, endfeet, and extracellular space (ECS) in response to cardiac-induced arteriole pulsations. Our model predicts that arteriole dilation compresses the PVS while expanding the overall endfoot sheath volume due to tangential stretch. Fluid exchange primarily occurs through inter-endfoot gaps, driven by pressure differences, rather than across the aquaporin-4 (AQP4) rich endfoot membrane. PVS stiffness critically modulates these dynamics: increased stiffness can reverse PVS volume changes and flow directionality, potentially minimizing fluid exchange at intermediate stiffness levels. While AQP4 has negligible impact on pulsation-driven mechanics, it significantly enhances osmotically driven fluid flow. These findings highlight the complex balance of forces governing gliovascular mechanics and suggest PVS composition strongly influences endfoot-parenchymal fluid exchange.

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