A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules

The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel networ...

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Bibliographic Details
Published in:The Journal of experimental medicine Vol. 212; no. 7; pp. 991 - 999
Main Authors: Aspelund, Aleksanteri, Antila, Salli, Proulx, Steven T, Karlsen, Tine Veronica, Karaman, Sinem, Detmar, Michael, Wiig, Helge, Alitalo, Kari
Format: Journal Article
Language:English
Published: United States 29.06.2015
Subjects:
Analysis of Variance
Animals
Brain - anatomy & histology
Brain - metabolism
Cerebrospinal Fluid - metabolism
Extracellular Fluid - metabolism
Fluorescent Antibody Technique
Galactosides
Green Fluorescent Proteins
Image Processing, Computer-Assisted
Indoles
Lymph Nodes - metabolism
Lymphatic System - anatomy & histology
Lymphatic System - metabolism
Macromolecular Substances - metabolism
Mice
Mice, Transgenic
Microscopy, Confocal
ISSN:1540-9538
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Summary:The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease.
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ISSN:1540-9538
DOI:10.1084/jem.20142290