Journal of neurotrauma
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Journal of neurotrauma · Jan 2018
Post-injury administration of galantamine reduces traumatic brain injury pathology and improves outcome.
Acetylcholine is an excitatory neurotransmitter in the central nervous system that plays a key role in cognitive function, including learning and memory. Previous studies have shown that experimental traumatic brain injury (TBI) reduces cholinergic neurotransmission, decreases evoked release of acetylcholine, and alters cholinergic receptor levels. Galantamine (U. ⋯ Specifically, significant improvements in the Morris water maze, novel object recognition, and context-specific fear memory tasks were observed in injured animals treated with galantamine. Although messenger RNAs for both M1 (Nos2, TLR4, and IL-12ß) and M2 (Arg1, CCL17, and Mcr1) microglial phenotypes were elevated post-TBI, galantamine treatment did not alter microglial polarization tested 24 h and 6 days post-injury. Taken together, these findings support the further investigation of galantamine as a treatment for TBI.
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Journal of neurotrauma · Jan 2018
Age at First Exposure to Repetitive Head Impacts Is Associated with Smaller Thalamic Volumes in Former Professional American Football Players.
Thalamic atrophy has been associated with exposure to repetitive head impacts (RHI) in professional fighters. The aim of this study is to investigate whether or not age at first exposure (AFE) to RHI is associated with thalamic volume in symptomatic former National Football League (NFL) players at risk for chronic traumatic encephalopathy (CTE). Eighty-six symptomatic former NFL players (mean age = 54.9 ± 7.9 years) were included. ⋯ The effect of AFE on right thalamic volume was almost twice as strong as the effect of total years of play. Our findings confirm previous reports of an association between thalamic volume and exposure to RHI. They suggest further that younger AFE may result in smaller thalamic volume later in life.
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Journal of neurotrauma · Jan 2018
Concussion alters the functional brain processes of visual attention and working memory.
Millions of North Americans sustain a concussion or a mild traumatic brain injury annually, and are at risk of cognitive, emotional, and physical sequelae. Although functional MRI (fMRI) studies have provided an initial framework for examining functional deficits induced by concussion, particularly working memory and attention, the temporal dynamics underlying these deficits are not well understood. We used magnetoencephalography (MEG), a modality with millisecond temporal resolution, in conjunction with a 1-back visual working memory (VWM) paradigm using scenes from everyday life to characterize spatiotemporal functional differences at specific VWM stages, in adults had had or had not had a recent concussion. ⋯ Parietal hypoactivation, starting at 60 ms during encoding, was correlated with symptom severity, possibly linked to impaired top-down attentional processing. Hyperactivation in the scene-selective occipitotemporal areas, the medial temporal complex, specifically the right hippocampus and orbitofrontal areas during encoding and/or recognition, lead us to posit inefficient but compensatory visuoperceptual, relational, and retrieval processing. Although injuries sustained after the concussion were considered "mild," these data suggest that they can have prolonged effects on early attentional and VWM processes.
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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.