Journal of neurotrauma
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Journal of neurotrauma · Jan 2017
TBI induces alterations in cortical glutamate uptake without a reduction in GLT-1 protein expression.
We hypothesize that the primary mechanism for removal of glutamate from the extracellular space is altered after traumatic brain injury (TBI). To evaluate this hypothesis, we initiated TBI in adult male rats using a 2.0 atm lateral fluid percussion injury (LFPI) model. In the ipsilateral cortex and hippocampus, we found no differences in expression of the primary glutamate transporter in the brain (GLT-1) 24 h after TBI. ⋯ Exploratory studies using an inhibitor of Akt suggest selective activation of kinases in LFPI versus controls. Ingenuity pathway analyses of implicated kinases from our network model found apoptosis and cell death pathways as top functions in acute LFPI. Taken together, our data suggest diminished activity of glutamate transporters in the prefrontal cortex, with no changes in protein expression of the primary glutamate transporter GLT-1, and global alterations in signaling networks that include serine-threonine kinases that are known modulators of glutamate transport activity.
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Journal of neurotrauma · Jan 2017
Comparative StudyStrong correlation of genome-wide expression after traumatic brain injury in vitro and in vivo implicates a role for SORLA.
The utility of in vitro models of traumatic brain injury (TBI) depends on their ability to recapitulate the in vivo TBI cascade. In this study, we used a genome-wide approach to compare changes in gene expression at several time points post-injury in both an in vitro model and an in vivo model of TBI. We found a total of 2073 differentially expressed genes in our in vitro model and 877 differentially expressed genes in our in vivo model when compared to noninjured controls. ⋯ We confirmed downregulation of SORLA expression in organotypic hippocampal slice cultures by immunohistochemistry and Western blotting and present preliminary data from human tissue that is consistent with these experimental results. Together, these data suggest that the in vitro model of TBI used in this study strongly recapitulates the in vivo TBI pathobiology and is well suited for future mechanistic or therapeutic studies. The data also suggest the possible involvement of SORLA in the post-traumatic cascade linking TBI to AD.
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Journal of neurotrauma · Jan 2017
Early and Persistent Dendritic Hypertrophy in the Basolateral Amygdala Following Experimental Diffuse Traumatic Brain Injury.
In the pathophysiology of traumatic brain injury (TBI), the amygdala remains understudied, despite involvement in processing emotional and stressful stimuli associated with anxiety disorders, such as post-traumatic stress disorder (PTSD). Because the basolateral amygdala (BLA) integrates inputs from sensory and other limbic structures coordinating emotional learning and memory, injury-induced changes in circuitry may contribute to psychiatric sequelae of TBI. This study quantified temporal changes in dendritic complexity of BLA neurons after experimental diffuse TBI, modeled by midline fluid percussion injury. ⋯ However, the BLA was relatively spared from neuropathology, demonstrated by an absence of argyrophilic accumulation over time, in contrast to other brain regions. These data suggest an early and persistent enhancement of dendritic complexity within the BLA after a single diffuse TBI. Increased dendritic complexity would alter information processing into and through the amygdala, contributing to emotional symptoms post-TBI, including PTSD.
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Current thinking views mild head impact (i.e., subconcussion) as an underrecognized phenomenon that has the ability to cause significant current and future detrimental neurological effects. Repeated mild impacts to the head, however, often display no observable behavioral deficits based on standard clinical tests, which may lack sensitivity. The current study investigates the effects of subconcussive impacts from soccer heading with innovative measures of vestibular function and walking stability in a pre- 0-2 h, post- 24 h post-heading repeated measures design. ⋯ Medial-lateral trunk orientation displacement and velocity during treadmill walking increased immediately after mild head impact for the heading group compared with controls. Controls showed an improvement in mBESS scores over time, indicating a learning effect, which was not observed with the heading group. These results suggest that mild head impact leads to a transient dysfunction in vestibular processing, which deters walking stability during task performance.
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Journal of neurotrauma · Jan 2017
Use of Transcranial Doppler in Patients with Severe Traumatic Brain Injuries.
Severe traumatic brain injuries (TBI) are associated with a high rate of mortality and disability. Transcranial Doppler (TCD) sonography permits a noninvasive measurement of cerebral blood flow. The purpose of this study is to determine the usefulness of TCD in patients with severe TBI. ⋯ Patients with hypoperfusion have a poor prognosis. Patients with vasospasm have a high incidence of mortality and severe disability. TCD is useful in determining early prognosis.