The perivascular pathways for influx of cerebrospinal fluid are most efficient in the midbrain

Clin Sci (Lond). 2017 Nov 13;131(22):2745-2752. doi: 10.1042/CS20171265. Print 2017 Nov 15.


Although there are no conventional lymphatic vessels in the brain, fluid and solutes drain along basement membranes (BMs) of cerebral capillaries and arteries towards the subarachnoid space and cervical lymph nodes. Convective influx/glymphatic entry of the cerebrospinal fluid (CSF) into the brain parenchyma occurs along the pial-glial BMs of arteries. This project tested the hypotheses that pial-glial BM of arteries are thicker in the midbrain, allowing more glymphatic entry of CSF. The in vivo MRI and PET images were obtained from a 4.2-year-old dog, whereas the post-mortem electron microscopy was performed in a 12-year-old dog. We demonstrated a significant increase in the thickness of the pial-glial BM in the midbrain compared with the same BM in different regions of the brain and an increase in the convective influx of fluid from the subarachnoid space. These results are highly significant for the intrathecal drug delivery into the brain, indicating that the midbrain is better equipped for convective influx/glymphatic entry of the CSF.

Keywords: CSF; convective influx; glymphatic; vascular basement membranes.

MeSH terms

  • Animals
  • Arteries / ultrastructure
  • Basement Membrane / ultrastructure
  • Cerebrospinal Fluid / metabolism*
  • Dogs
  • Endothelium / ultrastructure
  • Magnetic Resonance Imaging
  • Mesencephalon / blood supply*
  • Mesencephalon / ultrastructure
  • Muscle, Smooth / ultrastructure
  • Neuroglia / ultrastructure
  • Pia Mater / ultrastructure
  • Positron-Emission Tomography
  • Time Factors