title: Early brain injury alters the blood-brain barrier phenotype in parallel with β-amyloid and cognitive changes in adulthood.
abstract: Clinical studies suggest that traumatic brain injury (TBI) hastens cognitive decline and development of neuropathology resembling brain aging. Blood-brain barrier (BBB) disruption following TBI may contribute to the aging process by deregulating substance exchange between the brain and blood. We evaluated the effect of juvenile TBI (jTBI) on these processes by examining long-term alterations of BBB proteins, β-amyloid (Aβ) neuropathology, and cognitive changes. A controlled cortical impact was delivered to the parietal cortex of male rats at postnatal day 17, with behavioral studies and brain tissue evaluation at 60 days post-injury (dpi). Immunoglobulin G extravasation was unchanged, and jTBI animals had higher levels of tight-junction protein claudin 5 versus shams, suggesting the absence of BBB disruption. However, decreased P-glycoprotein (P-gp) on cortical blood vessels indicates modifications of BBB properties. In parallel, we observed higher levels of endogenous rodent Aβ in several brain regions of the jTBI group versus shams. In addition at 60 dpi, jTBI animals displayed systematic search strategies rather than relying on spatial memory during the water maze. Together, these alterations to the BBB phenotype after jTBI may contribute to the accumulation of toxic products, which in turn may induce cognitive differences and ultimately accelerate brain aging.
authors.affiliation: Department of Pediatrics, Loma Linda University, Loma Linda, CA 92354, USA.
authors.forename: Viorela
authors.initials: V
authors.lastname: Pop
authors.forename: Dane W
authors.initials: DW
authors.lastname: Sorensen
authors.forename: Joel E
authors.initials: JE
authors.lastname: Kamper
authors.forename: David O
authors.initials: DO
authors.lastname: Ajao
authors.forename: M Paul
authors.initials: MP
authors.lastname: Murphy
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Head
authors.forename: Richard E
authors.initials: RE
authors.lastname: Hartman
authors.forename: Jérôme
authors.initials: J
authors.lastname: Badaut
mesh_terms: D000375:Aging; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000293:injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D062507:Claudin-5 / Q000235:genetics / Q000378:metabolism; D003071:Cognition; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D062507:Claudin-5; C491510:Cldn5 protein, rat; D007074:Immunoglobulin G