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Large blood vessels entering the CNS are surrounded by perivascular spacesthat communicate with the cerebrospinal fluid and, at their termini, with theinterstitial space. Solutes and particles can translocate along theseperivascular conduits, reportedly in both directions. Recently, this prompted arenewed interest in the intrathecal therapy delivery route for CNS-targetedtherapeutics. However, the extent of the CNS coverage by the perivascularsystem is unknown, making the outcome of drug administration to the CSFuncertain. We traced the translocation of model macromolecules from the CSFinto the CNS of rats and non-human primates. Conduits transportingmacromolecules were found to extend throughout the parenchyma from bothexternal and internal (fissures) CNS boundaries, excluding ventricles, in largenumbers, on average ca. 40 channels per mm2 in rats and non-human primates. Thehigh density and depth of extension of the perivascular channels suggest thatthe perivascular route can be suitable for delivery of therapeutics toparenchymal targets throughout the CNS.

The Configuration of the Perivascular System Transporting Macromolecules in the CNS (PREPRINT)