Abstract
The brain lacks a traditional lymphatic system for metabolite clearance. The existence of a “glymphatic system” where metabolites are removed from the brain’s extracellular space by convective exchange between interstitial fluid (ISF) and cerebrospinal fluid (CSF) along the paravascular spaces (PVS) around cerebral blood vessels has been controversial. While recent work has shown clear evidence of directional flow of CSF in the PVS in anesthetized mice, the driving force for the observed fluid flow remains elusive. The heartbeat-driven peristaltic pulsation of arteries has been proposed as a probable driver of directed CSF flow. In this study, we use rigorous fluid dynamic simulations to provide a physical interpretation for peristaltic pumping of fluids. Our simulations match the experimental results and show that arterial pulsations only drive oscillatory motion of CSF in the PVS. The observed directional CSF flow can be explained by naturally occurring and/or experimenter-generated pressure differences.
Highlights
(of order 0.01 mmHg/mm) can account for the net forward movement observed experimentally. These results suggest that the observed directional movement of cerebrospinal fluid (CSF) in the paravascular spaces (PVS) is generated by naturally occurring and/or experimenter-generated pressure differences, but not by arterial pulsations
In this study we test the “peristaltic pumping” hypothesis, by using simulations of fluid dynamics to understand what experimental measurements tell us about bulk flow
We were able to improve upon previously published computational models aimed at studying the flow of CSF in the PVS8–10,25, using the detailed anatomical and physiological information from the experiments by Mestre et al.[7]
Summary
(of order 0.01 mmHg/mm) can account for the net forward movement observed experimentally. These results suggest that the observed directional movement of CSF in the PVS is generated by naturally occurring and/or experimenter-generated pressure differences, but not by arterial pulsations.
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