Journal of neurotrauma
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Journal of neurotrauma · Jul 2017
Applying systems biology methodology to identify genetic factors possibly associated with recovery after traumatic brain injury.
Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality worldwide. It is linked with a number of medical, neurological, cognitive, and behavioral sequelae. The influence of genetic factors on the biology and related recovery after TBI is poorly understood. ⋯ Overall, this study demonstrates the use of a systems biology-based approach to identify unique/novel genes or sets of genes important to the recovery process. Findings from this systems biology-based approach provide additional insight into the potential impact of genetic variants on the underlying complex biological processes important to TBI recovery and may inform the development of empirical genetic-related studies for TBI. Future studies that combine systems biology methodology and genomic, proteomic, and epigenetic approaches are needed in TBI.
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Journal of neurotrauma · Jul 2017
Outcome Trends Following US Military Concussive Traumatic Brain Injury.
Care for US military personnel with combat-related concussive traumatic brain injury (TBI) has substantially changed in recent years, yet trends in clinical outcomes remain largely unknown. Our prospective longitudinal studies of US military personnel with concussive TBI from 2008-2013 at Landstuhl Regional Medical Center in Germany and twp sites in Afghanistan provided an opportunity to assess for changes in outcomes over time and analyze correlates of overall disability. We enrolled 321 active-duty US military personnel who sustained concussive TBI in theater and 254 military controls. ⋯ Thus, across multiple cohorts of US military personnel with combat-related concussion, 6-12 month outcomes have improved only modestly and are often poor. Future focus on early depression and PTSD after concussive TBI appears warranted. Adverse outcomes are incompletely explained, however, and additional studies with prospective collection of data on acute injury severity and polytrauma, as well as reduced attrition before follow-up will be required to fully address the root causes of persistent disability after wartime injury.
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Journal of neurotrauma · Jul 2017
Trajectories and Risk-Factors for Posttraumatic Stress Symptoms Following Pediatric Concussion.
A substantial minority of children experience post-traumatic stress symptoms (PTSS) following injury. Research indicates variation in the trajectory of PTSS following pediatric injury, but investigation of PTSS following concussion has assumed homogeneity. This study aimed to identify differential trajectories of PTSS following pediatric concussion and to investigate risk factors, including acute post-concussive symptoms (PCS), associated with these trajectories. ⋯ Higher acute PCS and prior diagnosis of depression or anxiety both significantly increased predicted probability of recovering trajectory group membership. These findings establish that most children are resilient to PTSS following concussion, but that PTSS do occur acutely in a substantial minority of children. The study indicates mental health factors, particularly PTSS, depression, and anxiety, should be considered integral to models of concussion management and treatment.
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Journal of neurotrauma · Jul 2017
Inter-Subject Variability of Axonal Injury in Diffuse Traumatic Brain Injury.
Traumatic brain injury (TBI) is a leading cause of cognitive morbidity worldwide for which reliable biomarkers are needed. Diffusion tensor imaging (DTI) is a promising biomarker of traumatic axonal injury (TAI); however, existing studies have been limited by a primary reliance on group-level analytic methods not well suited to account for inter-subject variability. In this study, 42 adults with TBI of at least moderate severity were examined 3 months following injury and compared with 35 healthy controls. ⋯ In moderate-to-severe TBI, there is substantial inter-subject variation in TAI, with extent strongly correlated to post-traumatic deficits in processing speed. Significant group-level effects do not necessarily represent consistent effects at the individual level. Better accounting for inter-subject variability in neurobiological manifestations of TBI may substantially improve the ability to detect and classify patterns of injury.
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Hippocampal-dependent deficits in learning and memory formation are a prominent feature of traumatic brain injury (TBI); however, the role of the hippocampus in cognitive dysfunction after concussion (mild TBI) is unknown. We therefore investigated functional and structural changes in the swine hippocampus following TBI using a model of head rotational acceleration that closely replicates the biomechanics and neuropathology of closed-head TBI in humans. We examined neurophysiological changes using a novel ex vivo hippocampal slice paradigm with extracellular stimulation and recording in the dentate gyrus and CA1 occurring at 7 days following non-impact inertial TBI in swine. ⋯ Input-output curves demonstrated an elevated excitatory post-synaptic potential (EPSP) output for a given fiber volley input in injured versus sham animals, suggesting a form of homeostatic plasticity that manifested as a compensatory response to decreased axonal function in post-synaptic regions. These data indicate that closed-head rotational acceleration-induced TBI, the common cause of concussion in humans, may induce significant alterations in hippocampal circuitry function that have not resolved at 7 days post-injury. This circuitry dysfunction may underlie some of the post-concussion symptomatology associated with the hippocampus, such as post-traumatic amnesia and ongoing cognitive deficits.