title: Correlations between blood-brain barrier disruption and neuroinflammation in an experimental model of penetrating ballistic-like brain injury.
abstract: Abstract Blood-brain barrier (BBB) disruption is a pathological hallmark of severe traumatic brain injury (TBI) and is associated with neuroinflammatory events contributing to brain edema and cell death. The goal of this study was to elucidate the profile of BBB disruption after penetrating ballistic-like brain injury (PBBI) in conjunction with changes in neuroinflammatory markers. Brain uptake of biotin-dextran amine (BDA; 3 kDa) and horseradish peroxidase (HRP; 44 kDa) was evaluated in rats at 4 h, 24 h, 48 h, 72 h, and 7 days post-PBBI and compared with the histopathologic and molecular profiles for inflammatory markers. BDA and HRP both displayed a uniphasic profile of extravasation, greatest at 24 h post-injury and which remained evident out to 48 h for HRP and 7 days for BDA. This profile was most closely associated with markers for adhesion (mRNA for intercellular adhesion molecule-1) and infiltration of peripheral granulocytes (mRNA for matrix metalloproteinase-9 [MMP-9] and myeloperoxidase staining). Improvement of BBB dysfunction coincided with increased expression of markers implicated in tissue remodeling and repair. The results of this study reveal a uniphasic and gradient opening of the BBB after PBBI and suggest MMP-9 and resident inflammatory cell activation as candidates for future neurotherapeutic intervention after PBBI.
authors.affiliation: Walter Reed Army Institute of Research, Center for Military Psychiatry and Neuroscience , Branch of Brain Trauma Neuroprotection and Neurorestoration, Silver Spring, Maryland.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Cunningham
authors.forename: Casandra M
authors.initials: CM
authors.lastname: Cartagena
authors.forename: Xi-Chun M
authors.initials: XC
authors.lastname: Lu
authors.forename: Melissa
authors.initials: M
authors.lastname: Konopko
authors.forename: Jitendra R
authors.initials: JR
authors.lastname: Dave
authors.forename: Frank C
authors.initials: FC
authors.lastname: Tortella
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Shear
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000473:pathology / Q000503:physiopathology*; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology*; D020197:Head Injuries, Penetrating / Q000473:pathology / Q000503:physiopathology*; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley