Journal of neurotrauma
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Journal of neurotrauma · Sep 2009
Apolipoprotein E4 as a predictor of outcomes in pediatric mild traumatic brain injury.
The epsilon4 allele of the apolipoprotein E (APOE) gene has been linked to negative outcomes among adults with traumatic brain injury (TBI) across the spectrum of severity, with preliminary evidence suggesting a similar pattern among children. This study investigated the relationship of the APOE epsilon4 allele to outcomes in children with mild TBI. Participants in this prospective, longitudinal study included 99 children with mild TBI between the ages of 8 and 15 recruited from consecutive admissions to Emergency Departments at two large children's hospitals. ⋯ Those with an epsilon4 allele exhibited better performance than children without an epsilon4 allele on a test of constructional skill, but the groups did not differ on any other neuropsychological tests. Children with and without an epsilon4 allele also did not differ on measures of post-concussive symptoms. Overall, the findings suggest that the APOE epsilon4 allele is not consistently related to the outcomes of mild TBI in children.
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Journal of neurotrauma · Sep 2009
Validation of serum markers for blood-brain barrier disruption in traumatic brain injury.
The blood-brain barrier (BBB), which prevents the entry into the central nervous system (CNS) of most water-soluble molecules over 500 Da, is often disrupted after trauma. Post-traumatic BBB disruption may have important implications for prognosis and therapy. Assessment of BBB status is not routine in clinical practice because available techniques are invasive. ⋯ ROC analysis demonstrated a significant relationship between Q(A) and serum S100B concentrations at 12 h after TBI (AUC = 0.800; SE 0.147, 95% CI 0.511-1.089). Using an S100B concentration cutoff of 0.027 ng=ml, specificity for abnormal Q(A) was 90% or higher at each time point. We conclude that serum S100B concentrations accurately indicate BBB dysfunction at 12 h after TBI.
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Journal of neurotrauma · Sep 2009
Systemic sepsis exacerbates mild post-traumatic brain injury in the rat.
The development of sepsis in patient suffering from traumatic brain injury (TBI) represents a frequent complication that has been associated with worsened global and neurological outcome. In an effort to better characterize the influence of sepsis following TBI, we developed an in vivo model of combined TBI and sepsis in the rat by coupling two validated models: (1) Controlled Cortical Impact (CCI) and (2) Cecal Ligation and Puncture (CLP). Possible contributing effects of sepsis on post-traumatic outcome were evaluated as mortality rate, body weight change, neurological motor (beam balance), cognitive (Morris water maze [MWM] for memory and learning) function, histopathological damage (lesion volume, cell counts in the CA1 and CA3 hippocampal areas), and morphological indices of inflammation (activated microglia and astrocytes) for the 14-day study period. ⋯ The histological counterpart was represented by a cortical lesion in the area of impact at 14 days post-injury, associated with cell loss in the CA1 and CA3 hippocampal regions, and scarce infiltration of microglia. The superimposition of sepsis on this mild TBI model resulted in worsening of post-injury mortality and weight loss, significant exacerbation of post-injury motor deficit and cognitive impairments, and further exacerbation of neuronal cell death in the CA3 area together with over-expression and activation of microglial cells in the peri-lesional area. Altogether, our findings indicate that sepsis, when superimposed on TBI, exerts a negative effect on the evolution of post-traumatic damage.
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Journal of neurotrauma · Sep 2009
Neuropeptide Y modulates c-Fos protein expression in the cuneate nucleus and contributes to mechanical hypersensitivity following rat median nerve injury.
This study sought to investigate the effects of injury-induced neuropeptide Y (NPY) on c-Fos expression in the cuneate neurons and neuropathic pain after median nerve injury. Four weeks after median nerve transection (MNT), the injured nerves stimulated at low intensity (0.1 mA) expressed significantly less NPY-like immunoreactive (NPY-LI) fibers in the cuneate nucleus (CN) than those stimulated at high intensities (1.0 mA and 10 mA). Conversely, a significantly higher number of c-Fos-LI cells were observed in the CN in rats stimulated with 0.1 mA compared to those stimulated with 1.0 mA or 10 mA. ⋯ In rats with median nerve chronic constriction injury (CCI), intracerebroventricular injection of NPY aggravated mechanical allodynia and low-intensity stimulus-evoked c-Fos expression, both of which were reversed by injection of NPY receptor antagonist. However, thermal hyperalgesia was not affected by injection of these two reagents. Taken together, these findings suggest that more NPY release, following low-intensity electrical stimulation of the injured nerve, significantly induces c-Fos expression in the CTNs, which possibly provide the ascending thalamic transmission of neuropathic pain signals.
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Journal of neurotrauma · Sep 2009
Pediatric brain trauma outcome prediction using paired serum levels of inflammatory mediators and brain-specific proteins.
Many potential brain trauma biomarkers have been reported, but no previous study has described outcome prediction using combinations of biomarker levels. We aimed to investigate the outcome predictive values of multiple biomarkers from different mediator families and to determine whether combinations of two serum biomarkers may achieve higher outcome predictive values than individual biomarker levels. A prospective observational study was conducted involving 28 children requiring intensive care management following brain trauma. ⋯ None of the eight biomarkers assessed individually achieved an area under the ROC curve (AUC) of more than 0.95 for predicting unfavorable outcome, but five of the 20 biomarker pairs assessed had this high degree of outcome predictability. Two combinations using S100b as the "screening marker" and either L-selectin or IL-6 as the "varying marker" achieved an AUC of 0.98, and their specificity and sensitivity for unfavorable outcome prediction were 96% and 100%, respectively. Prognostic pairs combining serum levels of two biomarkers (inflammatory mediators and brain-specific proteins) offer better outcome predictive values for unfavorable outcome after childhood brain trauma than may be achieved using individual marker levels.