Correlations between Blood-Brain Barrier Disruption and Neuroinflammation in an Experimental Model of Penetrating Ballistic-Like Brain Injury

被引:26
作者
Cunningham, Tracy L. [1 ]
Cartagena, Casandra M. [1 ]
Lu, Xi-Chun M. [1 ]
Konopko, Melissa [1 ]
Dave, Jitendra R. [1 ]
Tortella, Frank C. [1 ]
Shear, Deborah A. [1 ]
机构
[1] Walter Reed Army Inst Res, Ctr Mil Psychiat & Neurosci, Branch Brain Trauma Neuroprotect & Neurorestorat, Silver Spring, MD 20910 USA
关键词
blood-brain barrier dysfunction; inflammation; penetrating brain injury; PBBI; traumatic brain injury; FLUID PERCUSSION INJURY; CENTRAL-NERVOUS-SYSTEM; INFLAMMATORY RESPONSE; FUNCTIONAL NEUROANATOMY; INSULA ACTIVATION; PREFRONTAL CORTEX; AFFECTED FORELIMB; INNATE SENSE; RAT MODEL; ANXIETY;
D O I
10.1089/neu.2013.2965
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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; 3kDa) and horseradish peroxidase (HRP; 44kDa) was evaluated in rats at 4h, 24h, 48h, 72h, 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 24h post-injury and which remained evident out to 48h 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.
引用
收藏
页码:505 / 514
页数:10
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