Journal of neurotrauma
-
Journal of neurotrauma · Dec 2009
Key role of sulfonylurea receptor 1 in progressive secondary hemorrhage after brain contusion.
An important but poorly understood feature of traumatic brain injury (TBI) is the clinically serious problem of spatiotemporal progression ("blossoming") of a hemorrhagic contusion, a phenomenon we term progressive secondary hemorrhage (PSH). Molecular mechanisms of PSH are unknown and efforts to reduce it by promoting coagulation have met with equivocal results. We hypothesized that PSH might be due to upregulation and activation of sulfonylurea receptor 1 (SUR1)-regulated NC(Ca-ATP) channels in capillary endothelial cells, predisposing to oncotic death of endothelial cells and catastrophic failure of capillary integrity. ⋯ Block of SUR1 using low-dose (non-hypoglycemogenic) glibenclamide largely eliminated PSH and capillary fragmentation, and was associated with a significant reduction in the size of the necrotic lesion and in preservation of neurobehavioral function. Antisense oligodeoxynucleotide against SUR1, administered after injury, reduced both SUR1 expression and PSH, consistent with a requirement for transcriptional upregulation of SUR1. Our findings provide novel insights into molecular mechanisms responsible for PSH associated with hemorrhagic contusions, and point to SUR1 as a potential therapeutic target in TBI.
-
Journal of neurotrauma · Dec 2009
Both hypoxemia and extreme hyperoxemia may be detrimental in patients with severe traumatic brain injury.
An association between hypoxemia and poor outcomes from traumatic brain injury (TBI) is well documented. However, it is unclear whether hyperoxygenation is beneficial. This registry-based analysis explores the relationship between early hypoxemia and hyperoxemia on outcome from moderate-to-severe TBI. ⋯ Logistic regression revealed an optimal Po(2) range (110-487 mm Hg), with an independent association observed between decreased survival and both hypoxemia (OR 0.54; 95% CI 0.42, 0.69; p < 0.001) and extreme hyperoxemia (OR 0.50; 95% CI 0.36, 0.71; p < 0.001). The association between hypoxemia and extreme hyperoxemia and worse outcomes was also present with use of "good outcomes" as the outcome variable (discharge to home, rehabilitation, jail, or psychiatric facility, or leaving against medical advice). We conclude that both hypoxemia and extreme hyperoxemia are associated with increased mortality and a decrease in good outcomes among TBI patients.
-
Journal of neurotrauma · Dec 2009
Randomized Controlled Trial Multicenter StudySafety and tolerability of cyclosporin a in severe traumatic brain injury patients: results from a prospective randomized trial.
Cyclosporin A (CsA) has recently been proposed for use in the early phase after traumatic brain injury (TBI), for its ability to preserve mitochondrial integrity in experimental brain injury models, and thereby provide improved behavioral outcomes as well as significant histological protection. The aim of this prospective, randomized, double-blind, dual-center, placebo-controlled trial was to evaluate the safety, tolerability, and pharmacokinetics of a single intravenous infusion of CsA in patients with severe TBI. Fifty adult severe TBI patients were enrolled over a 22-month period. ⋯ There were no significant differences in other mean laboratory values, or in the incidence of AEs at any other measured time point. Also, no significant difference was demonstrated for neurological outcome. Based on these results, we report a good safety profile of CsA infusion when given at the chosen dose of 5 mg/kg, infused over 24 h, during the early phase after severe head injury in humans, with the aim of neuroprotection.
-
Journal of neurotrauma · Dec 2009
Randomized Controlled Trial Multicenter StudyThe citicoline brain injury treatment (COBRIT) trial: design and methods.
Traumatic brain injury (TBI) is a major cause of death and disability. In the United States alone approximately 1.4 million sustain a TBI each year, of which 50,000 people die, and over 200,000 are hospitalized. Despite numerous prior clinical trials no standard pharmacotherapy for the treatment of TBI has been established. ⋯ The primary outcome consists of a set of measures that will be analyzed as a composite measure using a global test procedure at 90 days. The measures comprise the following core battery: the California Verbal Learning Test II; the Controlled Oral Word Association Test; Digit Span; Extended Glasgow Outcome Scale; the Processing Speed Index; Stroop Test part 1 and Stroop Test part 2; and Trail Making Test parts A and B. Secondary outcomes include survival, toxicity, and rate of recovery.
-
Journal of neurotrauma · Dec 2009
ReviewTreatment for depression after traumatic brain injury: a systematic review.
The aim of this systematic review was to critically evaluate the evidence on interventions for depression following traumatic brain injury (TBI) and provide recommendations for clinical practice and future research. We reviewed pharmacological, other biological, psychotherapeutic, and rehabilitation interventions for depression following TBI from the following data sources: PubMed, CINAHL, PsycINFO, ProQuest, Web of Science, and Google Scholar. We included studies written in English published since 1980 investigating depression and depressive symptomatology in adults with TBI; 658 articles were identified. ⋯ This systematic review documents that there is a paucity of randomized controlled trials for depression following TBI. Serotonergic antidepressants and cognitive behavioral interventions appear to have the best preliminary evidence for treating depression following TBI. More research is needed to provide evidence-based treatment recommendations for depression following TBI.