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

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Aspelund , A , Antila , S , Proulx , S T , Karlsen , T V , Karaman , S , Detmar , M , Wiig , H & Alitalo , K 2015 , ' A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules ' , Journal of Experimental Medicine , vol. 212 , no. 7 , pp. 991-999 . https://doi.org/10.1084/jem.20142290

Title: A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules
Author: Aspelund, Aleksanteri; Antila, Salli; Proulx, Steven T.; Karlsen, Tine Veronica; Karaman, Sinem; Detmar, Michael; Wiig, Helge; Alitalo, Kari
Contributor: University of Helsinki, Research Programs Unit
University of Helsinki, ETH, Swiss Federal Institute of Technology Zurich
University of Helsinki, Research Programs Unit
Date: 2015-06-29
Language: eng
Number of pages: 9
Belongs to series: Journal of Experimental Medicine
ISSN: 0022-1007
URI: http://hdl.handle.net/10138/298960
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.
Subject: ALZHEIMERS-DISEASE
ENDOTHELIAL-CELL
VEGF RECEPTOR-3
VESSELS
BLOOD
RAT
LYMPHANGIOGENESIS
VISUALIZATION
MECHANISMS
CLEARANCE
3112 Neurosciences
3124 Neurology and psychiatry
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