Glymphatic solute transport does not require bulk flow.

Mahdi Asgari,Vartan Kurtcuoglu,Diane De Zélicourt

doi:10.1038/srep38635

Mahdi Asgari, Vartan Kurtcuoglu + Show 1 more

Open Access

https://doi.org/10.1038/srep38635

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Abstract

Observations of fast transport of fluorescent tracers in mouse brains have led to the hypothesis of bulk water flow directed from arterial to venous paravascular spaces (PVS) through the cortical interstitium. At the same time, there is evidence for interstitial solute transport by diffusion rather than by directed bulk fluid motion. It has been shown that the two views may be consolidated by intracellular water flow through astrocyte networks combined with mainly diffusive extracellular transport of solutes. This requires the presence of a driving force that has not been determined to date, but for which arterial pulsation has been suggested as the origin. Here we show that arterial pulsation caused by pulse wave propagation is an unlikely origin of this hypothetical driving force. However, we further show that such pulsation may still lead to fast para-arterial solute transport through dispersion, that is, through the combined effect of local mixing and diffusion in the para-arterial space.

Highlights

Observations of fast transport of fluorescent tracers in mouse brains have led to the hypothesis of bulk water flow directed from arterial to venous paravascular spaces (PVS) through the cortical interstitium
We interrogated the first model to evaluate whether arterial pulsation may induce bulk flow in the PVS
The first one was created to test whether arterial pulsations, which have been suggested as possible driving mechanism for bulk flow, can convey solutes at rates demonstrated by tracer studies[2,22,23,24]

Summary

Introduction

Observations of fast transport of fluorescent tracers in mouse brains have led to the hypothesis of bulk water flow directed from arterial to venous paravascular spaces (PVS) through the cortical interstitium. It has been shown that the two views may be consolidated by intracellular water flow through astrocyte networks combined with mainly diffusive extracellular transport of solutes This requires the presence of a driving force that has not been determined to date, but for which arterial pulsation has been suggested as the origin. We have shown previously that under the assumption of a para-arterial to para-venous driving force, the observed fast transport of solutes can be explained by bulk water motion, provided that there is substantial intracellular water flow through astrocytes[7] It has been suggested, but not demonstrated, that arterial pulsation could generate the required driving force[8,9]. Much rather than being the origin of bulk flow, we demonstrate that arterial pulsation may lead to fast paravascular solute transport by dispersion

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