Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid

Nature. 2019 Aug;572(7767):62-66. doi: 10.1038/s41586-019-1419-5. Epub 2019 Jul 24.

Abstract

Recent work has shown that meningeal lymphatic vessels (mLVs), mainly in the dorsal part of the skull, are involved in the clearance of cerebrospinal fluid (CSF), but the precise route of CSF drainage is still unknown. Here we reveal the importance of mLVs in the basal part of the skull for this process by visualizing their distinct anatomical location and characterizing their specialized morphological features, which facilitate the uptake and drainage of CSF. Unlike dorsal mLVs, basal mLVs have lymphatic valves and capillaries located adjacent to the subarachnoid space in mice. We also show that basal mLVs are hotspots for the clearance of CSF macromolecules and that both mLV integrity and CSF drainage are impaired with ageing. Our findings should increase the understanding of how mLVs contribute to the neuropathophysiological processes that are associated with ageing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / pathology
  • Aging / physiology
  • Animals
  • Cerebrospinal Fluid / metabolism*
  • Endothelial Cells / cytology
  • Endothelial Cells / pathology
  • Female
  • Forkhead Transcription Factors / metabolism
  • Glymphatic System / anatomy & histology*
  • Glymphatic System / cytology
  • Glymphatic System / pathology
  • Glymphatic System / physiology*
  • Homeodomain Proteins / metabolism
  • Lymphatic Vessels / anatomy & histology*
  • Lymphatic Vessels / cytology
  • Lymphatic Vessels / pathology
  • Lymphatic Vessels / physiology*
  • Lymphedema / metabolism
  • Lymphedema / pathology
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Skull Base / anatomy & histology*
  • Subarachnoid Space / anatomy & histology
  • Time Factors
  • Tumor Suppressor Proteins / metabolism
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-3 / metabolism

Substances

  • Forkhead Transcription Factors
  • Homeodomain Proteins
  • Tumor Suppressor Proteins
  • Vascular Endothelial Growth Factor A
  • mesenchyme fork head 1 protein
  • prospero-related homeobox 1 protein
  • Vascular Endothelial Growth Factor Receptor-3