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The inhibitors of apoptosis (IAPs) are emerging as key proteins in the control of cell death. In this study, we evaluated the expression and subcellular distribution of the antiapoptotic protein X‐linked IAP (XIAP), and its interactions with the XIAP‐associated factor 1 (XAF1) in neonatal rat brain following hypoxia‐ischemia (HI). HI triggered the mitochondrial release of cytochrome c, Smac/DIABLO, and caspase 3 activation. Confocal microscopy detected XIAP‐specific immunofluorescence in the cytoplasm under normal condition, which exhibited a diffuse distribution at 6 h post‐HI and by 12 h the majority of XIAP was redistributed into the nucleus. XIAP nuclear translocation was confirmed by subcellular fractionations and by expressing FLAG‐tagged XIAP in primary cortical neurons. Over‐expression of XIAP significantly reduced, whereas XIAP gene silencing further enhanced cell death, demonstrating a specific requirement of cytoplasmic XIAP for cell survival. An elevated level of cytosolic XIAP was also evident under the conditions of neuroprotection by fibroblast growth factor‐1. XAF1 expression was increased temporally and there was increased nuclear co‐localization with XIAP in hypoxic‐ischemic cells. XIAP co‐immunoprecipitated > 9‐fold XAF1 protein concurrent with decreased association with caspases 9 and 3. This is evidenced by the enhanced caspase 3 activity and neuronal death. Our findings implicate XIAP nuclear translocation in neuronal death and point to a novel mechanism in the regulation of hypoxic‐ischemic brain injury.

Background: Many post-traumatic epilepsy (PTE) patients become resistant to medications. Nervous stimulation as a treatment for drug-resistant epilepsy (DRE) is an active area of clinical investigation.Objective: To summarize methods, reported seizure control outcome measures, and adverse events from blinded, randomized control trials (RCTs) for selected invasive brain stimulation (IBS) and non-invasive brain stimulation (NIBS) treatment options in patients with DRE.Methods: PubMed was searched for articles from 1995-2014, using search terms related to the topics of interest. Available relevant articles reporting the outcomes of interest were identified and data was extracted. Articles in the reference lists of relevant articles and clinicaltrials.gov were also referenced.Results: Eleven articles were analyzed with a total of 795 patients identified. Studies showed that select nervous stimulation treatments significantly reduced seizure frequency in patients with DRE.

OBJECTIVE Traumatic brain injury (TBI) is independently associated with deep vein thrombosis (DVT) and pulmonary embolism (PE). Given the numerous studies of civilian closed-head injury, the Brain Trauma Foundation recommends venous thromboembolism chemoprophylaxis (VTC) after severe TBI. No studies have specifically examined this practice in penetrating brain injury (PBI). Therefore, the authors examined the safety and effectiveness of early VTC after PBI with respect to worsening intracranial hemorrhage and DVT or PE. METHODS The Kandahar Airfield neurosurgery service managed 908 consults between January 2010 and March 2013. Eighty of these were US active duty members with PBI, 13 of whom were excluded from analysis because they presented with frankly nonsurvivable CNS injury or they died during initial resuscitation. This is a retrospective analysis of the remaining 67 patients. RESULTS Thirty-two patients received early VTC and 35 did not. Mean time to the first dose was 24 hours. Fifty-two patients had blast-related PBI and 15 had gunshot wounds (GSWs) to the head. The incidence of worsened intracranial hemorrhage was 16% after early VTC and 17% when it was not given, with the relative risk approaching 1 (RR = 0.91). The incidence of DVT or PE was 12% after early VTC and 17% when it was not given (RR = 0.73), though this difference was not statistically significant. CONCLUSIONS Early VTC was safe with regard to the progression of intracranial hemorrhage in this cohort of combat-related PBI patients. Data in this study suggest that this intervention may have been effective for the prevention of DVT or PE but not statistically significantly so. More research is needed to clarify the safety and efficacy of this practice.