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Open Access 01-01-2019 | Original Paper

Rapid lymphatic efflux limits cerebrospinal fluid flow to the brain

Authors: Qiaoli Ma, Miriam Ries, Yann Decker, Andreas Müller, Chantal Riner, Arno Bücker, Klaus Fassbender, Michael Detmar, Steven T. Proulx

Published in: Acta Neuropathologica | Issue 1/2019

Abstract

The relationships between cerebrospinal fluid (CSF) and brain interstitial fluid are still being elucidated. It has been proposed that CSF within the subarachnoid space will enter paravascular spaces along arteries to flush through the parenchyma of the brain. However, CSF also directly exits the subarachnoid space through the cribriform plate and other perineural routes to reach the lymphatic system. In this study, we aimed to elucidate the functional relationship between CSF efflux through lymphatics and the potential influx into the brain by assessment of the distribution of CSF-infused tracers in awake and anesthetized mice. Using near-infrared fluorescence imaging, we showed that tracers quickly exited the subarachnoid space by transport through the lymphatic system to the systemic circulation in awake mice, significantly limiting their spread to the paravascular spaces of the brain. Magnetic resonance imaging and fluorescence microscopy through the skull under anesthetized conditions indicated that tracers remained confined to paravascular spaces on the surface of the brain. Immediately after death, a substantial influx of tracers occurred along paravascular spaces extending into the brain parenchyma. We conclude that under normal conditions a rapid CSF turnover through lymphatics precludes significant bulk flow into the brain.

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Title: Rapid lymphatic efflux limits cerebrospinal fluid flow to the brain
Authors: Qiaoli Ma
Miriam Ries
Yann Decker
Andreas Müller
Chantal Riner
Arno Bücker
Klaus Fassbender
Michael Detmar
Steven T. Proulx
Publication date: 01-01-2019
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 1/2019
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-018-1916-x

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Rapid lymphatic efflux limits cerebrospinal fluid flow to the brain

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