4.6 Article

Astrocyte endfeet may theoretically act as valves to convert pressure oscillations to glymphatic flow

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ROYAL SOC
DOI: 10.1098/rsif.2023.0050

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cerebrospinal fluid; interstitial fluid; pressure oscillation; pressure valve; glymphatic system

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The glymphatic system, a cerebrospinal fluid transport system in the brain, has been associated with waste clearance, neurodegenerative diseases, and acute neurological disorders. While valves are important in other low-pressure fluid pathways to ensure flow direction, no valves have been found in the glymphatic system. This study proposes that astrocyte endfeet may act as valves using an elastic mechanism.
The glymphatic system of cerebrospinal fluid transport through the perivascular spaces of the brain has been implicated in metabolic waste clearance, neurodegenerative diseases and in acute neurological disorders such as stroke and cardiac arrest. In other biological low-pressure fluid pathways such as in veins and the peripheral lymphatic system, valves play an important role in ensuring the flow direction. Though fluid pressure is low in the glymphatic system and directed bulk flow has been measured in pial and penetrating perivascular spaces, no valves have yet been identified. Valves, which asymmetrically favour forward flow to backward flow, would imply that the considerable oscillations in blood and ventricle volumes seen in magnetic resonance imaging could cause directed bulk flow. Here, we propose that astrocyte endfeet may act as such valves using a simple elastic mechanism. We combine a recent fluid mechanical model of viscous flow between elastic plates with recent measurements of in vivo elasticity of the brain to predict order of magnitude flow-characteristics of the valve. The modelled endfeet are effective at allowing forward while preventing backward flow.

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