Journal of neurotrauma
-
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.
-
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.
-
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.
-
Journal of neurotrauma · May 2019
Rapid Repeat Exposure to Subthreshold Trauma Causes Synergistic Axonal Damage and Functional Deficits in the Visual Pathway in a Mouse Model.
We examined the effect of repeat exposure to a non-damaging insult on central nervous system axons using the optic projection as a model. The optic projection is attractive because its axons are spatially separated from the cell bodies, it is easily accessible, it is composed of long axons, and its function can be measured. We performed closed-system ocular neurotrauma in C57Bl/6 mice using bursts of 15 or 26-psi (pounds per square inch) overpressure air that caused no gross damage. ⋯ Therefore, repeat mild trauma within an interinjury interval of 1 min or less causes synergistic axon damage, whereas mild trauma repeated at a longer interinjury interval causes additive, cumulative damage. The synergistic damage may underlie the high incidence of traumatic brain injury and traumatic optic neuropathy in blast-injured service members given that explosive blasts are multiple injury events that occur in a very short time span. This study also supports the use of the VEP as a biomarker for traumatic optic neuropathy.
-
Journal of neurotrauma · May 2019
Proteomic Analysis and Biochemical Correlates of Mitochondrial Dysfunction following Low-Intensity Primary Blast Exposure.
Service members during military actions or combat training are frequently exposed to primary blasts by weaponry. Most studies have investigated moderate or severe brain injuries from blasts generating overpressures >100 kPa, whereas understanding the pathophysiology of low-intensity blast (LIB)-induced mild traumatic brain injury (mTBI) leading to neurological deficits remains elusive. Our recent studies, using an open-field LIB-induced mTBI mouse model with a peak overpressure at 46.6 kPa, demonstrated behavioral impairments and brain nanoscale damages, notably mitochondrial and axonal ultrastructural changes. ⋯ With observations of proteomic changes, we found LIB-induced oxidative stress associated with mitochondrial dysfunction mainly at 7 and 30 DPI. These dysfunctions included impaired fission-fusion dynamics, diminished mitophagy, decreased oxidative phosphorylation, and compensated respiration-relevant enzyme activities. Insights on the early pathogenesis of primary LIB-induced brain damage provide a template for further characterization of its chronic effects, identification of potential biomarkers, and targets for intervention.