Journal of neurotrauma
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Journal of neurotrauma · Jul 2014
Inhibition of Src Family Kinases Protects Hippocampal Neurons and Improves Cognitive Function after Traumatic Brain Injury.
Traumatic brain injury (TBI) is often associated with intracerebral and intraventricular hemorrhage. Thrombin is a neurotoxin generated at bleeding sites fater TBI and can lead to cell death and subsequent cognitive dysfunction via activation of Src family kinases (SFKs). ⋯ Systemic administration of the SFK inhibitor, PP2, immediately after moderate TBI blocks ROCK1 expression, protects hippocampal CA2/3 neurons, and improves spatial memory function. These data suggest the possibility that inhibiting SFKs after TBI might improve clinical outcomes.
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Journal of neurotrauma · Jul 2014
Transport mode to level I and II trauma centers and survival of pediatric patients with traumatic brain injury.
The use of helicopter emergency medical services (EMS) for pediatric trauma patients is an issue of debate. We investigated the association of helicopter transport with survival of pediatric patients with traumatic brain injury (TBI). We conducted a retrospective cohort study of pediatric patients with TBI who were transported to level I and II trauma centers and were registered in the National Trauma Data Bank (NTDB) between 2009 and 2011. ⋯ Multivariable logistic regression analysis demonstrated an association of helicopter transport with increased survival (OR, 2.35; 95% CI, 1.30-4.25; ARR 5.36%). This again persisted after propensity score matching (OR 2.56; 95% CI 1.28-5.11; ARR 6.14). Pediatric patients with TBI transported to level I and II trauma centers had improved survival in comparison with similar patients transported via ground EMS.
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Journal of neurotrauma · Jul 2014
Using the Olfactory System as an in vivo Model to Study Traumatic Brain Injury and Repair.
Loss of olfactory function is an early indicator of traumatic brain injury (TBI). The regenerative capacity and well-defined neural maps of the mammalian olfactory system enable investigations into the degeneration and recovery of neural circuits after injury. Here, we introduce a unique olfactory-based model of TBI that reproduces many hallmarks associated with human brain trauma. ⋯ Behavioral experiments measured 4 days after impact also demonstrated loss of olfactory function, yet following a 30-day recovery period, we observed a significant improvement in olfactory function and partial recovery of olfactory circuitry, despite the persistence of TBI markers. Interestingly, by using the M71-IRES-tauLacZ reporter line to track OSN organization, we further determined that inducing neural activity during the recovery period with intense odor conditioning did not enhance the recovery process. Together, these data establish the mouse olfactory system as a new model to study TBI, serving as a platform to understand neural disruption and the potential for circuit restoration.
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Journal of neurotrauma · Jul 2014
Activation of NF-κB Mediates Astrocyte Swelling and Brain Edema in Traumatic Brain Injury.
Brain edema and associated increased intracranial pressure are major consequences of traumatic brain injury (TBI). While astrocyte swelling (cytotoxic edema) represents a major component of the brain edema in the early phase of TBI, its mechanisms are unclear. One factor known to be activated by trauma is nuclear factor-κB (NF-κB). ⋯ By contrast, traumatized astrocyte cultures derived from NF-κB Tg mice showed no swelling. We also found increased astrocytic NF-κB activation and brain water content in rats after FPI, while BAY 11-7082 significantly reduced such effects. Our findings strongly suggest that activation of astrocytic NF-κB represents a key element in the process by which cytotoxic brain edema occurs after TBI.
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Journal of neurotrauma · Jul 2014
Randomized Controlled TrialExternal validation of the CRASH and IMPACT prognostic models in severe traumatic brain injury.
An accurate prognostic model is extremely important in severe traumatic brain injury (TBI) for both patient management and research. Clinical prediction models must be validated both internally and externally before they are considered widely applicable. Our aim is to independently externally validate two prediction models, one developed by the Corticosteroid Randomization After Significant Head injury (CRASH) trial investigators, and the other from the International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) group. ⋯ Using the CRASH CT model, the predicted 14 day mortality of 46.6% approximated the observed outcome, whereas the predicted 6 month unfavorable outcome was an overestimate at 74.8%. Overall, both the CRASH and IMPACT models showed good discrimination, with AUCs ranging from 0.80 to 0.89, and good overall calibration. We conclude that both the CRASH and IMPACT models satisfactorily predicted outcome in our patients with severe TBI.