Journal of neurotrauma
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Journal of neurotrauma · Oct 2013
A Prospective Evaluation of the Temporal Matrix Metalloproteinase Response after Severe Traumatic Brain Injury in Humans.
Abstract Accumulating pre-clinical data suggests that matrix metalloproteinase (MMP) expression plays a critical role in the pathophysiology of secondary brain injury. We conducted a prospective multimodal monitoring study in order to characterize the temporal MMP response after severe traumatic brain injury (TBI) in eight critically ill humans and its relationship with outcomes. High-cutoff, cerebral microdialysis (n=8); external ventricular drainage (n=3); and arterial and jugular venous bulb catheters were used to collect microdialysate, cerebrospinal fluid, and arterial and jugular bulb blood over 6 days. ⋯ Mean microdialysate levels of MMP-8 also rose with increasing intracranial pressure (ICP), whereas those of MMP-7 decreased with increasing cerebral perfusion pressure (CPP). Significant changes in the mean microdialysate concentrations of MMP-1, -2, -3, and -9 and MMP-1, -2, -3, -7, and -9 also occurred with increases in microdialysate glucose and the lactate/pyruvate ratio, respectively. These results imply that monitoring of MMPs following severe TBI in humans is feasible, and that their expression may be associated with clinical outcomes, ICP, CPP, and cerebral metabolism.
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Journal of neurotrauma · Oct 2013
Improved Behavior, Motor, and Cognition Assessments in Neonatal Piglets.
The alterations of animal behavior after traumatic brain injury (TBI) can be subtle, and their quantitative characterization can present significant methodological challenges. Meeting these challenges is a critical need, because quantitative measures are required in studies that compare the efficacy of different clinical interventions. ⋯ Our composite porcine disability score was able to detect brain injury with a sensitivity of 100% and specificity of 85.7% at day +4 post-injury for n=8 injured and n=7 sham piglets and significantly correlated with the percent axonal injury in these animals (day +4: ρ=0.76, p=0.0011). A significant improvement over our previous assessments, this new porcine disability score has potential use in a wide variety of porcine disease and injury models.
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Journal of neurotrauma · Oct 2013
Cytokine Gene Polymorphisms and Outcome after Traumatic Brain Injury.
Clinical outcome after traumatic brain injury (TBI) is variable and cannot easily be predicted. There is increasing evidence to suggest that there may be genetic influences on outcome. Cytokines play an important role in mediating the inflammatory response provoked within the central nervous system after TBI. ⋯ In an initial screen of 11 cytokine gene single nucleotide polymorphisms (SNPs) previously associated with disease susceptibility or outcome (TNFA -238 and -308, IL6 -174, -572 and -597, IL1A -889, IL1B -31, -511 and +3953, and TGFB -509 and -800), TNFA -308 was identified as having a likely association. The TNFA -308 SNP was further evaluated, and a significant association was identified, with 39% of allele 2 carriers having an unfavorable outcome compared with 31% of non-carriers (adjusted odds ratio 1.67, confidence interval 1.19-2.35, p=0.003). These findings are consistent with experimental and clinical data suggesting that neuroinflammation has an impact on clinical outcome after TBI and that tumor necrosis factor alpha plays an important role in this process.
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Journal of neurotrauma · Oct 2013
Complexity Analysis of Resting State Magnetoencephalography Activity in Traumatic Brain Injury Patients.
Diagnosis of mild traumatic brain injuries (TBIs) has been difficult because of the absence of obvious focal brain lesions, using conventional computed tomography (CT) or magnetic resonance imaging (MRI) scans, in a large percentage of TBIs. One useful measure that can characterize potential tissue and neural network damage objectively is Lempel-Ziv complexity (LZC) applied to magnetoencephalography (MEG) signals. LZC is a model-independent estimator of system complexity that estimates the number of different patterns in a sequence. ⋯ Resting state MEG data were acquired, and the LZCs were analyzed across the whole brain. Our results indicated reduced complexity in multiple brain areas in TBI patients relative to the healthy controls. In addition, we detected several neuropsychological measures associated with motor responses, visual perception, and memory, correlated with LZC, which likely explains some of the cognitive deficits in TBI patients.
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Journal of neurotrauma · Oct 2013
Blood-Brain Barrier Dysfunction after Primary Blast Injury in vitro.
The incidence of blast-induced traumatic brain injury (bTBI) has increased substantially in recent military conflicts. However, the consequences of bTBI on the blood-brain barrier (BBB), a specialized cerebrovascular structure essential for brain homeostasis, remain unknown. In this study, we utilized a shock tube driven by compressed gas to generate operationally relevant, ideal pressure profiles consistent with improvised explosive devices (IEDs). ⋯ Compromised ZO-1 immunostaining identified a structural basis for BBB breakdown. After blast exposure, TEER remained significantly depressed 2 days post-injury, followed by spontaneous recovery to pre-injury control levels at day 3. This study is the first to report immediate disruption of an in vitro BBB model following primary blast exposure, which may be important for the development of novel helmet designs to help mitigate the effects of blast on the BBB.