Journal of neurotrauma
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Journal of neurotrauma · Apr 2019
ReviewNeuronal Enriched Extracellular Vesicle Proteins as Biomarkers for Traumatic Brain Injury.
Traumatic brain injury (TBI) is a major cause of injury-related death throughout the world and lacks effective treatment. Surviving TBI patients often develop neuropsychiatric symptoms, and the molecular mechanisms underlying the neuronal damage and recovery following TBI are not well understood. Extracellular vesicles (EVs) are membranous nanoparticles that are divided into exosomes (originating in the endosomal/multi-vesicular body [MVB] system) and microvesicles (larger EVs produced through budding of the plasma membrane). ⋯ EVs enriched for neuronal origin can be harvested from peripheral blood samples and their contents quantitatively examined as a window to follow potential changes occurring in brain. Recent studies suggest that the levels of exosomal proteins and microRNAs (miRNAs) may represent novel biomarkers to support the clinical diagnosis and potential response to treatment for neurological disorders. In this review, we focus on the biogenesis of EVs, their molecular composition, and recent advances in research of their contents as potential diagnostic tools for TBI.
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Journal of neurotrauma · Apr 2019
Randomized Controlled TrialRepetitive Transcranial Magnetic Stimulation with Resting-State Network Targeting for Treatment-Resistant Depression in Traumatic Brain Injury: A Randomized, Controlled, Double-Blinded Pilot Study.
Repetitive transcranial magnetic stimulation (rTMS) has demonstrated antidepressant efficacy but has limited evidence in depression associated with traumatic brain injury (TBI). Here, we investigate the use of rTMS targeted with individualized resting-state network mapping (RSNM) of dorsal attention network (DAN) and default mode network (DMN) in subjects with treatment-resistant depression associated with concussive or moderate TBI. The planned sample size was 50 with first interim analysis planned at 20, but only 15 were enrolled before the study was terminated for logistical reasons. ⋯ Active treatment led to increased sgACC-DMN connectivity (d = 1.55) and increased sgACC anti-correlation with the left- and right-sided stimulation sites (d = -1.26 and -0.69, respectively). This pilot study provides evidence that RSNM-targeted rTMS is feasible in TBI patients with depression. Given the dearth of existing evidence-based treatments for depression in this patient population, these preliminarily encouraging results indicate that larger controlled trials are warranted.
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Journal of neurotrauma · Apr 2019
ReviewExperimental Designs for Repeated Mild Traumatic Brain Injury: Challenges and Considerations.
Mild traumatic brain injury (mild TBI) is a growing public concern, as evidence mounts that even brain injuries classified as "mild" can result in persistent neurological dysfunction. Multiple brain injuries heighten the likelihood of worsened or more prolonged symptomatology and may trigger long-term neurodegeneration. Animal models provide a logical platform to identify key parameters, such as loading forces, duration between injuries, and number of injuries, which contribute to additive or synergistic damage after repeated mild TBI. ⋯ The complexity of designing studies of repeated TBI is discussed, including challenges of incorporating appropriate control groups, informative experimental design, and relevant outcome measures. We then feature studies that provide a well-controlled, within-study design varying either the number of injuries or the interinjury interval. Harnessing the power of experimental models of TBI to elucidate which injury parameters are critical contributors to acute and chronic damage after repeated injury can further efforts at prevention and provide improved models for testing mechanisms and therapeutic interventions.
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Journal of neurotrauma · Apr 2019
Observational StudyEffects of Brain Temperature on the Outcome of Patients with Traumatic Brain Injury: A Prospective Observational Study.
A prospective observational study collected temperature data from 51 patients in 11 neurosurgical centers and follow-up outcome information at 6 months in 49 patients. Brain temperature (Tbr) was measured directly by an intraventricular temperature sensor. Axillary temperature (Tax) and rectal temperature (Tre) were measured by electric thermometers. ⋯ Spontaneously extreme Tpeak in TBI represents both more serious injury on admission and worse prognosis, and Tvari might be used as a novel prognostic parameter in TBI. Brain temperature is therefore one of the critical indicators evaluating injury severity, prognostication, and monitoring in the management of TBI. This prospective observational study has been registered in ClinicalTrials.gov ( https://clinicaltrials.gov ), and the registration number is NCT03068143.
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Journal of neurotrauma · Apr 2019
Comparative Effectiveness of Surgery for Traumatic Acute Subdural Hematoma in an Aging Population.
There is uncertainty as to the optimal initial management of patients with traumatic acute subdural hematoma, leading to regional variation in surgical policy. This can be exploited to compare the effect of various management strategies and determine best practices. This article reports such a comparative effectiveness analysis of a retrospective observational cohort of traumatic acute subdural hematoma patients in two geographically distinct neurosurgical departments chosen for their - a-priori defined - diverging treatment preferences. ⋯ Mortality was lower in region A (37% vs. 45%, p = 0.29), as was unfavorable outcome (53% vs. 62%, p = 0.23). The strategy favoring surgical evacuation was associated with significantly lower odds of mortality (odds ratio [OR]: 0.43; 95% confidence interval [CI]: 0.21-0.88) and unfavorable outcome (OR: 0.53; 95% CI: 0.27-1.02) 3-9 months post-injury. Therefore, in the aging population of patients with acute subdural hematoma, a treatment strategy favoring emergency hematoma evacuation might be associated with lower odds of mortality and unfavorable outcome.