Journal of neurotrauma
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Journal of neurotrauma · Oct 2016
Microglial/macrophage polarization dynamics following traumatic brain injury.
Activated microglia and macrophages exert dual beneficial and detrimental roles after central nervous system injury, which are thought to be due to their polarization along a continuum from a classical pro-inflammatory M1-like state to an alternative anti-inflammatory M2-like state. The goal of the present study was to analyze the temporal dynamics of microglia/macrophage polarization within the lesion micro-environment following traumatic brain injury (TBI) using a moderate-level controlled cortical impact (CCI) model in mice. We performed a detailed phenotypic analysis of M1- and M2-like polarized microglia/macrophages, as well as nicotinamide adenine dinucleotide phosphate oxidase (NOX2) expression, through 7 days post-injury using real-time polymerase chain reaction (qPCR), flow cytometry and image analyses. ⋯ In a follow up study, we administered a selective NOX2 inhibitor, gp91ds-tat, to CCI mice starting at 24 h post-injury to investigate the relationship between NOX2 and M1-like/Mtran phenotypes. Delayed gp91ds-tat treatment altered M1-/M2-like balance in favor of the anti-inflammatory M2-like phenotype, and significantly reduced oxidative damage in neurons at 7 days post-injury. Therefore, our data suggest that despite M1-like and M2-like polarized microglia/macrophages being activated after TBI, the early M2-like response becomes dysfunctional over time, resulting in development of pathological M1-like and Mtran phenotypes driven by increased NOX2 activity.
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Journal of neurotrauma · Oct 2016
Non-contact rotational head injury produces transient cognitive deficits but lasting neuropathological changes.
Traumatic brain injury (TBI) caused by improvised explosive devices (IEDs) is a growing problem in military settings, but modeling this disease in rodents to pre-clinically evaluate potential therapeutics has been challenging because of inconsistency between models. Although the effects of primary blast wave injury have been extensively studied, little is known regarding the effects of noncontact rotational TBIs independent of the blast wave. To model this type of injury, we generated an air cannon system that does not produce a blast wave, but generates enough air pressure to cause rotational TBI. ⋯ Despite the transient nature of the behavioral deficits, increased levels of phosphorylated tau were observed at 2 and 8 weeks post-injury; however, this tau did not adopt typical pathological structures that have been observed in other TBI models that incorporate blast waves. This was possibly attributed to the fact that this injury was insufficient to induce changes in microglial activation, which was not affected at 2 or 8 weeks post-injury. Taken together, these data suggest that exposure to noncontact, rotational head injury only produces transient cognitive anomalies, but elicits some minor lasting neuropathological changes.
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Journal of neurotrauma · Oct 2016
Role of Pre-Morbid Factors and Exposure to Blast Mild Traumatic Brain Injury on Post-Traumatic Stress in United States Military Personnel.
Mild traumatic brain injury (mTBI), the signature injury of the recent wars in Afghanistan and Iraq, is a prevalent and potentially debilitating condition that is associated with symptoms of post-traumatic stress/post-traumatic stress disorder (PTS/PTSD). Prior mTBI, severity and type of injury (blast vs. non-blast), and baseline psychiatric illness are thought to impact mTBI outcomes. It is unclear if the severity of pre-morbid PTS/PTSD is a risk factor of post-injury levels of PTS and mTBI symptoms. ⋯ Pre-morbid PTS symptoms are associated with an increased risk for clinical levels of PTS following a subsequent mTBI. Symptom severity and positive radiologic findings may amplify this risk. At-risk personnel may benefit from early identification and intervention.
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Journal of neurotrauma · Oct 2016
Injury of the corticospinal tract in patients with mild traumatic brain injury: A diffusion tensor tractography study.
Motor weakness is an important sequela after traumatic brain injury (TBI). Although the majority of cases of TBI are classified as mild TBI, little is known about motor weakness in mild TBI. In this study, we attempted to investigate injury of the corticospinal tract (CST), an important neural tract for motor function, in patients with mild TBI, using diffusion tensor tractography (DTT). ⋯ On configurational analysis of DTT for the left CST in patient group A, 80% showed partial tearing at the subcortical white matter and 20% showed narrowing. We found that in terms of DTT parameters and configuration, a significant portion of patients with mild TBI showed injury of the CST. These results suggest that DTT could provide useful information in detecting injury of the CST, and evaluation of the CST using DTT would be necessary for patients who complain of hand weakness after mild TBI.