Juvenile traumatic brain injury induces long-term perivascular matrix changes alongside amyloid-beta accumulation

J Cereb Blood Flow Metab. 2014 Oct;34(10):1637-45. doi: 10.1038/jcbfm.2014.124. Epub 2014 Jul 23.

Abstract

In our juvenile traumatic brain injury (jTBI) model, emergence of cognitive dysfunctions was observed up to 6 months after trauma. Here we hypothesize that early brain injury induces changes in the neurovascular unit (NVU) that would be associated with amyloid-beta (Aβ) accumulation. We investigated NVU changes for up to 6 months in a rat jTBI model, with a focus on the efflux protein P-glycoprotein (P-gp) and on the basement membrane proteins perlecan and fibronectin, all known to be involved in Aβ clearance. Rodent-Aβ staining is present and increased after jTBI around cerebral blood microvessels, and the diameter of those is decreased by 25% and 34% at 2 and 6 months, respectively, without significant angiogenesis. P-glycoprotein staining in endothelium is decreased by 22% and parallels an increase of perlecan and fibronectin staining around cerebral blood vessels. Altogether, these results strongly suggest that the emergence of long-term behavioral dysfunctions observed in rodent jTBI may be related to endothelial remodeling at the blood-brain barrier alongside vascular dysfunction and altered Aβ trafficking. This study shows that it is important to consider jTBI as a vascular disorder with long-term consequences on cognitive functions.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / pathology
  • Brain / blood supply*
  • Brain / metabolism
  • Brain / pathology*
  • Brain Injuries / metabolism
  • Brain Injuries / pathology*
  • Fibronectins / analysis
  • Fibronectins / metabolism
  • Heparan Sulfate Proteoglycans / analysis
  • Heparan Sulfate Proteoglycans / metabolism
  • Male
  • Microcirculation
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Amyloid beta-Peptides
  • Fibronectins
  • Heparan Sulfate Proteoglycans
  • perlecan