Journal of neurotrauma
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Journal of neurotrauma · Jan 2018
SKELETAL MUSCLE ATROPHY AND DEGENERATION IN A MOUSE MODEL OF TRAUMATIC BRAIN INJURY.
Atrophy is thought to be a primary mode of muscle loss in neuromuscular injuries. The differential effects of central and peripheral injuries on atrophy and degeneration/regeneration in skeletal muscle tissue have not been well described. This study investigated skeletal muscle atrophy and degeneration/regeneration in an animal model of traumatic brain injury (TBI). ⋯ Injured soleus FAs were smaller than sham soleus (p = 0.02) and injured TA (p < 0.001). Mean CNs were higher in the TBI-injured TA than in other muscles. Differential TBI-induced atrophy and degeneration/regeneration in lower limb muscles suggests that muscle responses to cortical injury involve more complex changes than those observed with simple disuse atrophy.
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Journal of neurotrauma · Jan 2018
Elucidating pro-inflammatory cytokine responses following traumatic brain injury in a human stem cell model.
Cytokine mediated inflammation likely plays an important role in secondary pathology after traumatic brain injury (TBI). The aim of this study was to elucidate secondary cytokine responses in an in vitro enriched (>80%) human stem cell-derived neuronal model. We exposed neuronal cultures to pre-determined and clinically relevant pathophysiological levels of tumor necrosis factor-α (TNF), interleukin-6 (IL-6) and interleukin-1β (IL-1β), shown to be present in the inflammatory aftermath of TBI. ⋯ Importantly, these patterns are consistent with our in vivo (human) TBI data, thus validating our human stem cell-derived neuronal platform as a clinically useful reductionist model. Our data cumulatively suggest that IL-6 and TNF have direct actions, while the action of IL-1β on human neurons likely occurs indirectly through inflammatory cells. The hESC-derived neurons provide a valuable platform to model cytokine mediated inflammation and can provide important insights into the mechanisms of neuroinflammation after TBI.
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Journal of neurotrauma · Jan 2018
REPEATED EXPOSURE TO EXPERIMENTAL PAIN DIFFERENTIATES COMBAT TBI WITH AND WITHOUT PTSD.
Mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) are highly comorbid conditions that often co-occur with chronic pain. We have shown that women with PTSD subsequent to intimate partner violence show attenuated brain response to repeated experimental pain that was related to symptoms of avoidance. The aim of this study was to extend our past findings to males with combat trauma and to examine brain response to experimental pain in men with and without PTSD who sustained mTBI during combat. ⋯ The current study provides further evidence that repeated exposure to brief painful stimuli results in attenuation of insula activation over time in traumatized individuals. Further, in PTSD, AI shows greatest attenuation in those with the highest level of avoidance-a finding that was replicated across diverse samples. Thus, this mechanism may be a generalized mechanism of maladaptive response to experimental pain in those with significant trauma.
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Journal of neurotrauma · Jan 2018
Alterations in the timing of huperzine-A cerebral pharmacodynamics in the acute traumatic brain injury setting.
Traumatic brain injury (TBI) may affect the pharmacodynamics of centrally acting drugs. Paired-pulse transcranial magnetic stimulation (ppTMS) is a safe and noninvasive measure of cortical gamma-aminobutyric acid (GABA)-mediated cortical inhibition. Huperzine A (HupA) is a naturally occurring acetylcholinesterase inhibitor with newly discovered potent GABA-mediated antiepileptic capacity, which is reliably detected by ppTMS. ⋯ This was consistent with a quadratic trend comparison that projects HupA-mediated cortical inhibition to last longer in injured rats (p = 0.007). We show that 1) cortical GABA-mediated inhibition, as measured by ppTMS, decreases acutely post-TBI, 2) HupA restores lost post-TBI GABA-mediated inhibition, and 3) HupA-mediated enhancement of cortical inhibition is delayed post-TBI. The plausible reasons of the latter include 1) low HupA volume of distribution rendering HupA confined in the intravascular compartment, therefore vulnerable to reduced post-TBI cerebral perfusion, and 2) GABAR dysfunction and increased AChE activity post-TBI.
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Journal of neurotrauma · Jan 2018
Neurolipids and microRNA changes in blood following blast traumatic brain injury in mice: an exploratory study.
At present, accurate and reliable biomarkers to ascertain the presence, severity, or prognosis of blast traumatic brain injury (bTBI) are lacking. There is an urgent need to establish accurate and reliable biomarkers capable of mbTBI detection. Currently, there are no studies that identify changes in miRNA and lipids at varied severities of bTBI. ⋯ Plasma levels of brain-enriched miRNA, miR-127 were increased in all groups while let-7a, b, and g were reduced in the 17 × 3 and 20 psi groups, but let 7d was increased in the 17 psi group. The majority of the miRs and lipids are highly conserved across different species, making them attractive to explore and potentially employ as diagnostic markers. It is tempting to speculate that sphingolipids, miR-128, and the let-7 family could predict mTBI, while a combination of miR-484, miR-122, miR-148a, miR-130a, and miR-223 could be used to predict the overall status of injury following blast injury.