Journal of neurotrauma
-
Journal of neurotrauma · May 2014
Diffusion tensor imaging reveals white matter injury in a rat model of repetitive blast-induced traumatic brain injury.
Blast-induced traumatic brain injury (bTBI) is one of the most common combat-related injuries seen in U. S. military personnel, yet relatively little is known about the underlying mechanisms of injury. In particular, the effects of the primary blast pressure wave are poorly understood. ⋯ Computational statistical methods such as voxelwise analysis have shown promise in localizing and quantifying bTBI throughout the brain. In this study, we use voxelwise analysis of DTI to quantify white matter injury in a rat model of repetitive primary blast exposure. Our results show a significant increase in microstructural damage with a second blast exposure, suggesting that primary bTBI may sensitize the brain to subsequent injury.
-
Journal of neurotrauma · May 2014
Observational StudyFunctional Status Following Blast-Plus-Impact Complex Concussive Traumatic Brain Injury in Evacuated United States Military Personnel.
Fundamental questions remain unanswered about the longitudinal impact of blast-plus-impact complex traumatic brain injuries (TBI) from wars in Iraq and Afghanistan. This prospective, observational study investigated measures of clinical outcome in US military personnel evacuated to Landstuhl Regional Medical Center (LRMC) in Germany after such "blast-plus" concussive TBIs. Glasgow Outcome Scale-Extended assessments completed 6-12 months after injury indicated a moderate overall disability in 41/47 (87%) blast-plus TBI subjects and a substantial but smaller number (11/18, 61%, p=0.018) of demographically similar US military controls without TBI evacuated for other medical reasons. ⋯ Thus, in summary, high rates of PTSD and depression but not cognitive impairment or focal neurological deficits were observed 6-12 months after concussive blast-plus-impact complex TBI. Overall disability was substantially greater than typically reported in civilian non-blast concussive ("mild") patients with TBI, even with polytrauma. The relationship between these clinical outcomes and specific blast-related aspects of brain injuries versus other combat-related factors remains unknown.
-
Journal of neurotrauma · May 2014
Repeated Primary Blast Injury Causes Delayed Recovery, But Not Additive Disruption, in an In Vitro Blood-Brain Barrier Model.
Recent studies have demonstrated increased susceptibility to breakdown of the cerebral vasculature associated with repetitive traumatic brain injury. We hypothesized that exposure to two consecutive blast injuries would result in exacerbated damage to an in vitro model of the blood-brain barrier (BBB) compared with exposure to a single blast of the same severity. Contrary to our hypothesis, however, repeated mild or moderate primary blast delivered with a 24 or 72 h interval between injuries did not significantly exacerbate reductions in transendothelial electrical resistance (TEER) across a brain endothelial monolayer compared with sister cultures receiving a single exposure of the same intensity. ⋯ Similarly, recovery of hydraulic conductivity through the BBB was delayed by a second exposure. Extending the interinjury interval to 72 h, the effects of multiple injuries on the BBB were found to be independent given sufficient recovery time between consecutive exposures. Careful investigation of the effects of repeated blast on the BBB will help identify injury levels and a temporal window of vulnerability associated with BBB dysfunction, ultimately leading to improved strategies for protecting warfighters against repeated blast-induced disruption of the cerebral vasculature.
-
Journal of neurotrauma · May 2014
Comparative StudyComparison of the Effect of Minocycline and Simvastatin on Functional Recovery and Gene Expression in a Rat Traumatic Brain Injury Model.
The goal of this study was to compare the effects of minocycline and simvastatin on functional recovery and brain gene expression after a cortical contusion impact (CCI) injury. Dosage regimens were designed to provide serum concentrations in a rat model in the range obtained with clinically approved doses; minocycline 60 mg/kg q12h and simvastatin 10 mg/kg q12h for 72 h. Functional recovery was assessed using motor and spatial learning tasks and neuropathological measurements. ⋯ There was a minimal effect of simvastatin on gene expression 24 h after injury, with increasing effects at 72 h and 7 days. GOA identified a significant effect of simvastatin on inflammatory response at 72 h and 7 days. In conclusion, treatment with minocycline and simvastatin resulted in significant effects on gene expression in the brain reflecting adequate brain penetration without producing significant neurorestorative effects.
-
Journal of neurotrauma · May 2014
Old dog, new tricks: the attentional set-shifting test as a novel cognitive behavioral task after controlled cortical impact injury.
Cognitive impairment associated with prefrontal cortical dysfunction is a major component of disability in traumatic brain injury (TBI) survivors. Specifically, deficits of cognitive flexibility and attentional set-shifting are present across all levels of injury severity. Though alterations in spatial learning have been extensively described in experimental models of TBI, studies investigating more complex cognitive deficits are relatively scarce. ⋯ Further, injury severity-induced deficits in ED set-shifting and stimulus reversals, as well as increases in total response error rates and total set loss errors, were observed. These novel findings demonstrate executive function and behavioral flexibility deficits in our animal model of CCI injury and provide the impetus to integrate the AST in the standard neurotrauma behavioral battery to further evaluate cognitive dysfunction after TBI. Ongoing experiments in our laboratory are assessing AST performance after pharmacological and rehabilitative therapies post-TBI, as well as elucidating possible mechanisms underlying the observed neuropsychological deficits.