Outflow of cerebrospinal fluid is predominantly through lymphatic vessels and is reduced in aged mice

Cerebrospinal fluid (CSF) has been commonly accepted to drain through arachnoid projections from the subarachnoid space to the dural venous sinuses. However, a lymphatic component to CSF outflow has long been known. Here, we utilize lymphatic-reporter mice and high-resolution stereomicroscopy to cha...

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Bibliographic Details
Published in:Nature communications Vol. 8; no. 1; pp. 1434 - 13
Main Authors: Ma, Qiaoli, Ineichen, Benjamin V., Detmar, Michael, Proulx, Steven T.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 10.11.2017
Nature Publishing Group
Nature Portfolio
Subjects:
631/1647/245/2225
631/378/2607
692/698/1688/64
Age
Aging - physiology
Animals
Arachnoid
Arachnoid - physiology
Blood vessels
Brain
Brain - physiology
Cerebrospinal fluid
Cerebrospinal Fluid - physiology
Coloring Agents - administration & dosage
Female
Humanities and Social Sciences
Imaging techniques
Lymph nodes
Lymphatic system
Lymphatic System - physiology
Lymphatic Vessels - physiology
Mice
Mice, Inbred C57BL
Mice, Transgenic
multidisciplinary
Neuroimaging
Outflow
Rodents
Science
Science (multidisciplinary)
Sinus
Sinuses
Stereomicroscopy
Subarachnoid space
Tracers
Ventricle
Ventricles (cerebral)
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary:Cerebrospinal fluid (CSF) has been commonly accepted to drain through arachnoid projections from the subarachnoid space to the dural venous sinuses. However, a lymphatic component to CSF outflow has long been known. Here, we utilize lymphatic-reporter mice and high-resolution stereomicroscopy to characterize the anatomical routes and dynamics of outflow of CSF. After infusion into a lateral ventricle, tracers spread into the paravascular spaces of the pia mater and cortex of the brain. Tracers also rapidly reach lymph nodes using perineural routes through foramina in the skull. Using noninvasive imaging techniques that can quantify the transport of tracers to the blood and lymph nodes, we find that lymphatic vessels are the major outflow pathway for both large and small molecular tracers in mice. A significant decline in CSF lymphatic outflow is found in aged compared to young mice, suggesting that the lymphatic system may represent a target for age-associated neurological conditions. It is believed that the bulk of cerebrospinal fluid (CSF) drains through arachnoid projections from the subarachnoid space to the dural venous sinuses. Here the authors show that the major outflow pathway for CSF in mice are lymphatic vessels and that this drainage decreases as the mice age.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-017-01484-6