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The Configuration of the Perivascular System Transporting Macromolecules in the CNS.

Authors
  • Durcanova, Beata1
  • Appleton, Janine1
  • Gurijala, Nyshidha1
  • Belov, Vasily1, 2, 3
  • Giffenig, Pilar1
  • Moeller, Elisabeth1
  • Hogan, Matthew1
  • Lee, Fredella1
  • Papisov, Mikhail1, 2, 3
  • 1 Massachusetts General Hospital, Boston, MA, United States. , (United States)
  • 2 Harvard Medical School, Boston, MA, United States. , (United States)
  • 3 Shriners Hospitals for Children - Boston, Boston, MA, United States. , (United States)
Type
Published Article
Journal
Frontiers in Neuroscience
Publisher
Frontiers Media SA
Publication Date
Jan 01, 2019
Volume
13
Pages
511–511
Identifiers
DOI: 10.3389/fnins.2019.00511
PMID: 31191221
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Large blood vessels entering the CNS are surrounded by perivascular spaces that communicate with the cerebrospinal fluid and, at their termini, with the interstitial space. Solutes and particles can translocate along these perivascular conduits, reportedly in both directions. Recently, this prompted a renewed interest in the intrathecal therapy delivery route for CNS-targeted therapeutics. However, the extent of the CNS coverage by the perivascular system is unknown, making the outcome of drug administration to the CSF uncertain. We traced the translocation of model macromolecules from the CSF into the CNS of rats and non-human primates. Conduits transporting macromolecules were found to extend throughout the parenchyma from both external and internal (fissures) CNS boundaries, excluding ventricles, in large numbers, on average ca. 40 channels per mm2 in rats and non-human primates. The high density and depth of extension of the perivascular channels suggest that the perivascular route can be suitable for delivery of therapeutics to parenchymal targets throughout the CNS.

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