Journal of neurotrauma
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Journal of neurotrauma · Oct 2016
Minimal traumatic brain injury in mice - PAR-1 and thrombin related changes.
Minimal traumatic brain injury (mTBI) is partially defined by the existence of retrograde amnesia and is associated with microscopic bleeds containing activated coagulation factors. In a previous study, we have found that mTBI immediately releases thrombin-like activity in the brain, which induces amnesia by activating protease-activated receptor 1 (PAR-1) and blocking long-term potentiation (LTP). In the present study, we assessed the effects of mTBI on thrombin and PAR-1 levels in the brain using the same model. ⋯ Interestingly, the late elevation in thrombin-like activity was also associated with elevation of the major central nervous system thrombin inhibitor, protease nexin-1, 72 h post-mTBI (10%; p < 0.005). When thrombin was injected into brain ventricles, an increased sensitivity to seizure-like activity was detected at 72 h post-mTBI. The results are compatible with astrocyte activation post-mTBI resulting in increased thrombin secretion, PAR-1 expression, and seizure sensitivity.
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Journal of neurotrauma · Oct 2016
Minor Functional Deficits in Basic Response Patterns for Reinforcement following Frontal Traumatic Brain Injury in Rats.
Traumatic brain injury (TBI) is a major contributor to numerous psychiatric conditions and chronic behavioral dysfunction. Recent studies in experimental brain injury have begun to adopt operant methodologies to assess these deficits, all of which rely on the process of reinforcement. No studies have directly examined how reinforced behaviors are affected by TBI, however. ⋯ Further, injured rats were specifically impaired at lower response requirements on the progressive ratio. Taken together, these findings indicate that simple reinforced behaviors are mostly unaffected after TBI, except in the case of variable ratio schedules, but the altered performance on the higher-order progressive ratio schedule suggests changes involving motivation or potentially perseveration. These findings validate operant measures of more complex behaviors for brain injury, all of which rely on reinforcement and can be taken into consideration when adapting and developing novel functional assessments.
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Journal of neurotrauma · Oct 2016
The serum phosphorylated neurofilament heavy subunit as a predictive marker for outcome in adult patients after traumatic brain injury.
The serum phosphorylated neurofilament heavy subunit (pNF-H) is a nervous system-specific protein that is released from damaged neural tissue after traumatic brain injury (TBI). The aim of this study was to elucidate the usefulness of serum pNF-H as a predictive marker for the outcome of patients after TBI. Patients with TBI (Glasgow Coma Scale score of 13 or less on admission) were included. ⋯ The optimal cutoff value was 240 pg/mL, and the area under the curve in the receiver operating characteristic analysis was 0.930. The serum pNF-H value at 72 h after injury was correlated with an unfavorable outcome (vegetative state or death) at 6 months (p < 0.01) with a cutoff value of 80 pg/mL. Collectively, the results of this study indicate that the serum pNF-H value is a useful predictive marker for patient outcome after TBI.
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Journal of neurotrauma · Oct 2016
Randomized Controlled TrialCortical Thickness in Mild Traumatic Brain Injury.
Magnetic resonance imaging data were acquired at ∼24 h and ∼3 months post-injury on mild traumatic brain injury (mTBI; n = 75) and orthopedic injury (n = 60) cohorts. The mTBI subjects were randomly assigned to a treatment group with atorvastatin or a non-treatment mTBI group. The treatment group was further divided into drug and placebo subgroups. ⋯ Further analysis revealed significant cortical thinning only in the non-treatment group relative to the control group. In the follow-up, small regions with significant but subtle cortical thinning and thickening were seen in the frontal, temporal, and parietal lobes in the left hemisphere in the non-treatment group only. Our results indicate that cortical thickness could serve as a useful measure in identifying subtle changes in mTBI patients.
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Journal of neurotrauma · Oct 2016
Probenecid and N-acetylcysteine Prevent Loss of Intracellular Glutathione and Inhibit Neuronal Death after Mechanical Stretch Injury In Vitro.
Probenecid and N-acetylcysteine (NAC) can preserve intracellular levels of the vital antioxidant glutathione (GSH) via two distinct biochemical pathways. Probenecid inhibits transporter-mediated GSH efflux and NAC serves as a cysteine donor for GSH synthesis. We hypothesized that probenecid and NAC alone would maintain intracellular GSH concentrations and inhibit neuronal death after traumatic stretch injury, and that the drugs in combination would produce additive effects. ⋯ Interestingly, caspase 3 activity 24 h after mechanical trauma was more prominent in XX-neurons, and treatment effects (probenecid, NAC, and Pro-NAC) were observed in XX- but not XY-neurons; however, XY-neurons were ultimately more vulnerable to mechanical stretch-induced injury than their XX counterparts, as was evidenced by more neuronal death detected by LDH release and PI uptake. In addition, after stretch injury in HT22 hippocampal cells, both NAC and probenecid were highly effective at reducing oxidative stress detected by dichlorofluorescein fluorescence. These in vitro data support further testing of this drug combination in models of traumatic neuronal injury in vivo.