Magnetic resonance imaging of cerebrospinal fluid outflow after low-rate lateral ventricle infusion in mice

The anatomical routes for the clearance of cerebrospinal fluid (CSF) remain incompletely understood. However, recent evidence has given strong support for routes leading to lymphatic vessels. A current debate centers upon the routes through which CSF can access lymphatics, with evidence emerging for...

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Main Authors: Yann Decker, Jonas Krämer, Li Xin, Andreas Müller, Anja Scheller, Klaus Fassbender, Steven T. Proulx
Format: Article
Language:English
Published: American Society for Clinical investigation 2022-02-01
Series:JCI Insight
Subjects:
Online Access:https://doi.org/10.1172/jci.insight.150881
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author Yann Decker
Jonas Krämer
Li Xin
Andreas Müller
Anja Scheller
Klaus Fassbender
Steven T. Proulx
author_facet Yann Decker
Jonas Krämer
Li Xin
Andreas Müller
Anja Scheller
Klaus Fassbender
Steven T. Proulx
author_sort Yann Decker
collection DOAJ
description The anatomical routes for the clearance of cerebrospinal fluid (CSF) remain incompletely understood. However, recent evidence has given strong support for routes leading to lymphatic vessels. A current debate centers upon the routes through which CSF can access lymphatics, with evidence emerging for either direct routes to meningeal lymphatics or along cranial nerves to reach lymphatics outside the skull. Here, a method was established to infuse contrast agent into the ventricles using indwelling cannulae during imaging of mice at 2 and 12 months of age by magnetic resonance imaging. As expected, a substantial decline in overall CSF turnover was found with aging. Quantifications demonstrated that the bulk of the contrast agent flowed from the ventricles to the subarachnoid space in the basal cisterns. Comparatively little contrast agent signal was found at the dorsal aspect of the skull. The imaging dynamics from the 2 cohorts revealed that the contrast agent was cleared from the cranium through the cribriform plate to the nasopharyngeal lymphatics. On decalcified sections, we confirmed that fluorescently labeled ovalbumin drained through the cribriform plate and could be found within lymphatics surrounding the nasopharynx. In conclusion, routes leading to nasopharyngeal lymphatics appear to be a major efflux pathway for cranial CSF.
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spelling doaj.art-52e23287c5dc4c3e87a055da4224419a2022-12-22T03:38:17ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-02-0173Magnetic resonance imaging of cerebrospinal fluid outflow after low-rate lateral ventricle infusion in miceYann DeckerJonas KrämerLi XinAndreas MüllerAnja SchellerKlaus FassbenderSteven T. ProulxThe anatomical routes for the clearance of cerebrospinal fluid (CSF) remain incompletely understood. However, recent evidence has given strong support for routes leading to lymphatic vessels. A current debate centers upon the routes through which CSF can access lymphatics, with evidence emerging for either direct routes to meningeal lymphatics or along cranial nerves to reach lymphatics outside the skull. Here, a method was established to infuse contrast agent into the ventricles using indwelling cannulae during imaging of mice at 2 and 12 months of age by magnetic resonance imaging. As expected, a substantial decline in overall CSF turnover was found with aging. Quantifications demonstrated that the bulk of the contrast agent flowed from the ventricles to the subarachnoid space in the basal cisterns. Comparatively little contrast agent signal was found at the dorsal aspect of the skull. The imaging dynamics from the 2 cohorts revealed that the contrast agent was cleared from the cranium through the cribriform plate to the nasopharyngeal lymphatics. On decalcified sections, we confirmed that fluorescently labeled ovalbumin drained through the cribriform plate and could be found within lymphatics surrounding the nasopharynx. In conclusion, routes leading to nasopharyngeal lymphatics appear to be a major efflux pathway for cranial CSF.https://doi.org/10.1172/jci.insight.150881NeuroscienceVascular biology
spellingShingle Yann Decker
Jonas Krämer
Li Xin
Andreas Müller
Anja Scheller
Klaus Fassbender
Steven T. Proulx
Magnetic resonance imaging of cerebrospinal fluid outflow after low-rate lateral ventricle infusion in mice
JCI Insight
Neuroscience
Vascular biology
title Magnetic resonance imaging of cerebrospinal fluid outflow after low-rate lateral ventricle infusion in mice
title_full Magnetic resonance imaging of cerebrospinal fluid outflow after low-rate lateral ventricle infusion in mice
title_fullStr Magnetic resonance imaging of cerebrospinal fluid outflow after low-rate lateral ventricle infusion in mice
title_full_unstemmed Magnetic resonance imaging of cerebrospinal fluid outflow after low-rate lateral ventricle infusion in mice
title_short Magnetic resonance imaging of cerebrospinal fluid outflow after low-rate lateral ventricle infusion in mice
title_sort magnetic resonance imaging of cerebrospinal fluid outflow after low rate lateral ventricle infusion in mice
topic Neuroscience
Vascular biology
url https://doi.org/10.1172/jci.insight.150881
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