title: Juvenile traumatic brain injury induces long-term perivascular matrix changes alongside amyloid-beta accumulation.
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.
authors: Department of Pediatrics, Loma Linda University, Loma Linda, California, USA.
authors: Amandine
authors: A
authors: Jullienne
authors: Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA.
authors: Jill M
authors: JM
authors: Roberts
authors: Department of Pediatrics, Loma Linda University, Loma Linda, California, USA.
authors: Viorela
authors: V
authors: Pop
authors: Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA.
authors: M
authors: M
authors: Paul Murphy
authors: Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA.
authors: Elizabeth
authors: E
authors: Head
authors: Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA.
authors: Gregory J
authors: GJ
authors: Bix
authors: 1] Department of Pediatrics, Loma Linda University, Loma Linda, California, USA [2] Department of Physiology, Loma Linda University, Loma Linda, California, USA [3] CNRS UMR 5287, Bordeaux University, Bordeaux, France.
authors: Jérôme
authors: J
authors: Badaut
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D005353:Fibronectins / Q000032:analysis / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000032:analysis / Q000378:metabolism; D008297:Male; D008833:Microcirculation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D005353:Fibronectins; D019812:Heparan Sulfate Proteoglycans; C071927:perlecan