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

@article{Aspelund2015ADL,
  title={A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules},
  author={Aleksanteri Aspelund and Salli Antila and Steven T. Proulx and Tine Veronica Karlsen and Sinem Karaman and Michael Detmar and Helge Wiig and Kari Alitalo},
  journal={The Journal of Experimental Medicine},
  year={2015},
  volume={212},
  pages={991 - 999}
}
The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. [] Key Method 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…

Figures from this paper

Central nervous system has a lymphatic system: What's next?
TLDR
The presence of dural lymphatic vessels has finally been unveiled, revealing a novel pathway of mononuclear cell egress into the central nervous system parenchyma without breaking the blood–brain barrier.
Lymphatic vessels at the base of the mouse brain provide direct drainage to the periphery
A set of lymphatic vessels that wrap around the base of the mouse brain have been shown to drain fluid from the brain into the peripheral lymphatic system, and to exhibit a decline in function with
Lymphatic vessels at the base of the mouse brain provide direct drainage to the periphery
A set of lymphatic vessels that wrap around the base of the mouse brain have been shown to drain fluid from the brain into the peripheral lymphatic system, and to exhibit a decline in function with
Functional Meningeal Lymphatics and Cerebrospinal Fluid Outflow
TLDR
The role of functional meningeal lymphatics and cerebrospinal fluid outflow is highlighted andabolites and neurotoxins in this system may be excreted via this system and accumulate in the cervical lymph nodes.
Organ-specific lymphatic vasculature: From development to pathophysiology
Petrova and Koh discuss recent progress in understanding organ-specific specialization of lymphatic vasculature, such as discovery of meningeal lymphatic vasculature and perivascular brain lymphatic
A (delayed) history of the brain lymphatic system
It has been only recently that scientists come to realize the existence of a lymphatic system within the central nervous system. However, an Italian anatomist had already found and described the
The amazing brain drain
TLDR
It is demonstrated that central nervous system lymphatics develop in the mouse meninges during early postnatal periods and display remarkable plasticity in adult periods through manipulation of VEGF-C–VEGFR3 signaling.
Clearance of cerebrospinal fluid from the sacral spine through lymphatic vessels
Using a tracer-based approach with near-infrared fluorescence and magnetic resonance imaging in mice, the authors establish the concept of a cranial-to-caudal circulation of cerebrospinal fluid
How Do Meningeal Lymphatic Vessels Drain the CNS?
...
...

References

SHOWING 1-10 OF 58 REFERENCES
Integration of the subarachnoid space and lymphatics: Is it time to embrace a new concept of cerebrospinal fluid absorption?
TLDR
The objective of this paper is to review the key studies pertaining to the role of the lymphatic system in CSF absorption and consider a new conceptual foundation on which to base the understanding of disorders of the CSF system.
Is there a cerebral lymphatic system?
TLDR
The distances between much of the brain tissue and the CSF compartments are too great for efficient clearance by simple diffusion, particularly for large molecules (such as peptides and proteins) with low diffusion coefficients.
A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β
TLDR
An anatomically distinct clearing system in the brain that serves a lymphatic-like function is described and may have relevance for understanding or treating neurodegenerative diseases that involve the mis-accumulation of soluble proteins, such as amyloid β in Alzheimer's disease.
Lymphatic drainage of the brain and the pathophysiology of neurological disease
TLDR
Facilitating perivascular lymphatic drainage of amyloid-β (Aβ) in the elderly may prevent the accumulation of Aβ in the brain, maintain homeostasis and provide a therapeutic strategy to help avert cognitive decline in Alzheimer’s disease.
Lymphatic drainage of the cerebrospinal fluid from monkey spinal meninges with special reference to the distribution of the epidural lymphatics.
TLDR
The findings suggest that the epidural lymphatics are well developed on the dorsal side of the lower cervical spinal dura mater and may function as an absorptive pathway for the cerebrospinal fluid from the subarachnoidal space.
Topographic study on nerve-associated lymphatic vessels in the murine craniofacial region by immunohistochemistry and electron microscopy.
TLDR
The present findings suggest that the lymphatic system associated with the cranial nerves provides the pathway for transport of cerebrospinal fluid, tissue fluid, and free cells involved in immune response and tumor metastasis in the craniofacial region.
CSF drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology and immunological significance
TLDR
This study demonstrates the direct drainage of cerebrospinal fluid through the cribriform plate in anatomically defined channels which connect with the nasal lymphatics.
The function and structure of the cerebrospinal fluid outflow system
  • M. Pollay
  • Medicine
    Cerebrospinal Fluid Research
  • 2010
TLDR
The functional capabilities of the total CSF drainage system are presented, with evidence that the duality of the system is supported by the changes in fluid outflow dynamics in human and sub-human primates in hydrocephalus.
Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3
TLDR
It is shown that a soluble form of VEGFR-3 is a potent inhibitor of Vascular endothelial growth factor (VEGF)-C and VEGF-D signaling, and when expressed in the skin of transgenic mice, it inhibits fetal lymphangiogenesis and induces a regression of already formed lymphatic vessels, though the blood vasculature remains normal.
...
...