Journal of neurotrauma
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Journal of neurotrauma · May 2019
A Data-driven Approach to Unlikely, Possible, Probable, and Definite Acute Concussion Assessment.
Kutcher and Giza suggested incorporating levels of certainty in concussion diagnosis decisions. These guidelines were based on clinical experience rather than objective data. Therefore, we combined data-driven optimization with predictive modeling to identify which athletes are unlikely to have concussion and to classify remaining athletes as having possible, probable, or definite concussion with diagnostic certainty. ⋯ Baseline to post-injury change scores for the SAC, SCAT symptoms, and BESS were significantly different between acute possible and probable concussions and normal performances (p < 0.05). There were no consistent patterns in demographics across risk categories, although a greater proportion of concussions classified as unlikely were reported immediately compared with definite concussions (p < 0.05). Although clinical interpretation is still needed, our data-driven approach to concussion risk stratification provides a promising step toward evidence-based concussion assessment.
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Journal of neurotrauma · May 2019
Therapeutic effect of a novel fatty acid amide hydrolase inhibitor PF04457845 in the repetitive closed head injury mouse model.
Concussive traumatic brain injury (TBI) is the predominant type of brain injury in young adults and is a risk factor for the development of chronic traumatic encephalopathy and other neurodegenerative diseases late in life. Using a repetitive closed head injury mouse model, we found that treatment with PF04457845, a novel fatty acid amide hydrolase (FAAH) inhibitor that selectively elevated the brain levels of anandamide, improved locomotor function, learning, and memory in TBI mice examined by beam walk, Y-maze, and Morris water maze tests. The accumulation of microglia and astrocytes and the expression of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α), in the ipsilateral TBI mouse cortex and hippocampus were significantly reduced by drug treatment. ⋯ The improved locomotor function and working memory were partially mediated by activation of both cannabinoid (CB)1 and CB2 receptors, whereas the improvement on spatial learning and memory seemed to be CB1 receptor dependent. Interestingly, the blockage of PF04457845 on the reduced expression of synaptophysin, but not SNAP25 and α-CSP, was reversed by coadministration of the CB1 receptor antagonist. These results suggest that the therapeutic effect of PF04457845 is mediated by both cannabinoid receptor dependent and independent mechanisms, and selective inhibition of FAAH possesses a great potential for the treatment of TBI.
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Journal of neurotrauma · May 2019
Multicenter Study Comparative StudyComparison of Performance of Different Optimal Cerebral Perfusion Pressure Parameters for Outcome Prediction in Adult Traumatic Brain Injury: A Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study.
It has been postulated previously that individualized cerebral perfusion pressure (CPP) targets can be derived from cerebrovascular reactivity indices. Differences between real CPP and target CPP (named generically optimal CPP) has been linked to global outcome in adult traumatic brain injury (TBI). Different vascular reactivity indices can be utilized in the determination. ⋯ PRx- and RAC-based CPPopt performed similarly, with RAC parameters trending towards highest AUC values. PAx-based CPPopt parameters failed to reach significant associations with dichotomized outcomes at 6 to 12 months. CPPopt parameters derived from PRx and RAC appear similar in their overall ability for 6- to 12-month outcome prediction in moderate/severe adult TBI.
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Journal of neurotrauma · May 2019
Comprehensive Characterization of Cerebrovascular Dysfunction in Blast Traumatic Brain Injury Using Photoacoustic Microscopy.
Blast traumatic brain injury (bTBI) is a leading contributor to combat-related injuries and death. Although substantial emphasis has been placed on blast-induced neuronal and axonal injuries, co-existing dysfunctions in the cerebral vasculature, particularly the microvasculature, remain poorly understood. Here, we studied blast-induced cerebrovascular dysfunctions in a rat model of bTBI (blast overpressure: 187.8 ± 18.3 kPa). ⋯ This study is the most comprehensive assessment of cerebrovascular structure and physiology in response to blast exposure to date. The observed impairment in CVR can potentially cause cognitive decline due to the mismatch between cognitive metabolic demands and vessel's ability to dynamically respond to meet the demands. Also, the impaired CVR can lead to increased vulnerability of the brain to metabolic insults, including hypoxia and ischemia.
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Journal of neurotrauma · May 2019
Differences in PTSD Symptoms among Post-9/11 Veterans with Blast- and Non-blast Mild TBI.
The relationship between traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) has been difficult to disentangle, in part due to the commonality of incidents that can cause both conditions, as well as high rates of comorbidity between the two conditions. Inconsistent findings may be related to different study characteristics and types of mild TBI (mTBI) sustained (e.g., blast, non-blast). ⋯ As hypothesized, a between-groups analysis of covariance (ANCOVA) revealed that, after controlling for demographics, combat exposure, and prior trauma, PTSD symptoms among individuals with blast-related mTBI and combined blast and non-blast mTBI were significantly higher compared with non-blast-related mTBI and no TBI. These data suggest that blast-related mTBI is associated with more severe long-term PTSD symptoms.