Journal of neurotrauma
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Journal of neurotrauma · May 2019
Interhemispheric anatomical disconnection in disorders of consciousness patients.
In patients with disorder of consciousness (DOC), the corpus callosum (CC) and subcortical white matter (SWM) integrity were shown to discriminate between diagnostic categories. The aims of the study were: (1) to clarify the link between the integrity of CC and of SWM and the clinical status in DOC patients, disentangling the role played by the different brain injuries (traumatic or hemorrhagic brain injury); (2) to investigate the relationship between the CC integrity and the brain metabolism. We assessed the diagnostic accuracy of the CC and SWM integrity, using diffusion tensor imaging (DTI) and structural magnetic resonance imaging (sMRI), in a sample of DOC individuals, well balanced for diagnosis and etiology. ⋯ No significant diagnostic accuracy emerged for the CC sMRI evaluation and the SWM measures. Our results indicate that: (1) the degree of the interhemispherical anatomical disconnection is a marker of the level of consciousness independent from the type of brain injury; (2) CC alterations might be the consequence of the reduced brain metabolism. Remarkably, our results suggest that the functional interplay between the two hemispheres is linked tightly to the level of consciousness.
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Journal of neurotrauma · May 2019
Evaluation of Brain Response During Head Impact in Youth Athletes Using an Anatomically Accurate Finite Element Model.
During normal participation in football, players are exposed to repetitive subconcussive head impacts, or impacts that do not result in signs and symptoms of concussion. To better understand the effects of repetitive subconcussive impacts, the biomechanics of on-field head impacts and resulting brain deformation need to be well characterized. The current study evaluates local brain response to typical youth football head impacts using the atlas-based brain model (ABM), an anatomically accurate brain finite element (FE) model. ⋯ This was 1.5 times greater than the oblique impact location, which resulted in the lowest strain value of 0.12 for high magnitude impacts. Overall, higher strains resulted from a 95th percentile lateral impact (41.0g, 2556 rad/sec2) with two predominant axes of rotation than from a 95th percentile frontal impact (67.6g, 2641 rad/sec2) with a single predominant axis of rotation. These findings highlight the importance of accounting for directional dependence and relative contribution of axes of rotation when evaluating head impact response.
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Journal of neurotrauma · May 2019
Biophysical modeling suggests optimal drug combinations for improving the efficacy of GABA agonists after traumatic brain injuries.
Traumatic brain injuries (TBI) lead to dramatic changes in the surviving brain tissue. Altered ion concentrations, coupled with changes in the expression of membrane-spanning proteins, create a post-TBI brain state that can lead to further neuronal loss caused by secondary excitotoxicity. Several GABA receptor agonists have been tested in the search for neuroprotection immediately after an injury, with paradoxical results. ⋯ The likelihood of prolonged, excitotoxic depolarization block is further exacerbated by the extremely high levels of extracellular potassium seen after TBI. Our modeling results predict that the neuroprotective efficacy of GABA receptor agonists can be substantially enhanced when they are combined with NKCC1 co-transporter inhibitors. This suggests a rational, biophysically principled method for identifying drug combinations for neuroprotection after TBI.
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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
Evaluating Cerebrovascular Reactivity during the Early Symptomatic Phase of Sport Concussion.
Cerebrovascular reactivity (CVR) indexes the ability of blood vessels to respond to vasoactive stimuli and may be a sensitive biomarker of concussion. However, alterations in whole-brain CVR remain poorly understood during the early symptomatic phase of injury. In this study, CVR was assessed using blood-oxygenation-level dependent functional magnetic resonance imaging (BOLD fMRI) combined with a respiratory challenge paradigm; resting cerebral blood flow (CBF) was also evaluated using arterial spin labeling (ASL). ⋯ In addition, greater symptom severity was associated with greater reductions in BOLD response, with effects distributed throughout the brain. This study establishes fMRI with respiratory challenge as a robust method for assessing acute concussion-related alterations in CVR. Moreover, it highlights the importance of examining neurovascular response to physiological stressors after a concussion.