  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.
