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J Exp Med. 2015 Jun 29;212(7):991-9. doi: 10.1084/jem.20142290. Epub 2015 Jun 15.

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

Author information

1
Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, 00014 Helsinki, Finland Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, 00014 Helsinki, Finland.
2
Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH Zurich), CH-8093 Zurich, Switzerland.
3
Department of Biomedicine, University of Bergen, 5009 Bergen, Norway.
4
Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, 00014 Helsinki, Finland Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, 00014 Helsinki, Finland kari.alitalo@helsinki.fi.

Abstract

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.

PMID:
26077718
PMCID:
PMC4493418
DOI:
10.1084/jem.20142290
[Indexed for MEDLINE]
Free PMC Article

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