Stretch and flow at the gliovascular interface: High-fidelity modeling of astrocyte endfeet

• 成果类型: Article
• 署名作者: Causemann, Marius; Enger, Rune; Rognes, Marie E.
• 署名单位: University of Oslo; University of Oslo; National Hospital Norway
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2517059123
• 发表日期: 2026-03-17
• 页码: e2517059123
• 关键词: astrocyte endfeet; perivascular spaces; poroelasticity; digital twin; mechanics; EXTRACELLULAR-SPACE; brain; fluid; aquaporin-4; clearance; cells; mice

摘要

Astrocyte endfeet form a near-continuous sheath around the brain's vasculature, defining the perivascular spaces (PVS) that are crucial for brain fluid flow and solute transport. Yet, their precise physiological role remains poorly understood. Using electron microscopy data, we created a high-fidelity poroelastic computational model of an arteriole segment with surrounding endfeet and parenchyma to investigate tissue displacement and fluid flow within the PVS, endfeet, and extracellular space in response to blood vessel pulsations. Our model predicts that arteriole dilations compress the PVS while expanding the overall endfoot sheath volume due to tangential stretch. Moreover, 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 the PVS, for instance, due to vessel pathology or aging, would minimize or reverse fluid exchange at the gliovascular interface. While AQP4 mediated water movement has a negligible impact on pulsation-driven mechanics, it significantly enhances osmotically driven fluid flow. Overall, our findings elucidate the complex balance of forces governing gliovascular mechanics and suggest that PVS composition strongly influences endfoot-parenchymal fluid exchange.