Journal of neurotrauma
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Journal of neurotrauma · May 2019
Autonomic Dysfunction and Associations with Functional and Neurophysiological Outcome in Moderate/Severe Traumatic Brain Injury: A Scoping Review.
The quantification and objective documentation of autonomic dysfunction in traumatic brain injury (TBI) is neither well studied nor extensively validated. Most of the descriptions of autonomic dysfunction in the literature are in the form of vague non-specific clinical manifestations. Few studies propose the use of objective measures of assessing the extent of autonomic dysfunction to link them to the outcome of TBI. ⋯ A total of 2714 adult patients were studied. Although the nature of association between autonomic dysfunction and outcome is unclear, the objective quantification of autonomic dysfunction seems to be associated with global patient outcome and other neurophysiological measures. Further studies are needed to validate its use and explore the underlying molecular mechanisms of the described associations.
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Journal of neurotrauma · May 2019
Therapeutic effect of a novel fatty acid amide hydrolase inhibitor PF04457845 in the repetitive closed head injury mouse model.
Concussive traumatic brain injury (TBI) is the predominant type of brain injury in young adults and is a risk factor for the development of chronic traumatic encephalopathy and other neurodegenerative diseases late in life. Using a repetitive closed head injury mouse model, we found that treatment with PF04457845, a novel fatty acid amide hydrolase (FAAH) inhibitor that selectively elevated the brain levels of anandamide, improved locomotor function, learning, and memory in TBI mice examined by beam walk, Y-maze, and Morris water maze tests. The accumulation of microglia and astrocytes and the expression of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α), in the ipsilateral TBI mouse cortex and hippocampus were significantly reduced by drug treatment. ⋯ The improved locomotor function and working memory were partially mediated by activation of both cannabinoid (CB)1 and CB2 receptors, whereas the improvement on spatial learning and memory seemed to be CB1 receptor dependent. Interestingly, the blockage of PF04457845 on the reduced expression of synaptophysin, but not SNAP25 and α-CSP, was reversed by coadministration of the CB1 receptor antagonist. These results suggest that the therapeutic effect of PF04457845 is mediated by both cannabinoid receptor dependent and independent mechanisms, and selective inhibition of FAAH possesses a great potential for the treatment of TBI.
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Journal of neurotrauma · May 2019
Headache trigger sensitivity and avoidance after mild traumatic brain injury.
Most patients with primary headache disorders identify environmental stimuli (e.g., visual glare), situational factors (e.g., stress), physiological states (e.g., hormones), or activities (e.g., exercise) as triggers that elicit or worsen headache episodes. Headache triggers have not been previously studied in post-traumatic headache (PTH). The present study explored the frequency of headache triggers and their avoidance in PTH. ⋯ Headache severity was more associated with trigger sensitivity [F(2,49) = 13.45, p < 0.001] than trigger avoidance [F(2,47) = 2.97, p = 0.062]. In summary, the pattern of headache triggers in persistent PTH after mild TBI appears somewhat different from that in primary headache disorders, with mental exertion emerging as uniquely important. Pervasive avoidance of mental exertion to prevent headaches (cogniphobia) might be a worthwhile behavioral intervention target after mild TBI.
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Journal of neurotrauma · May 2019
Matrix Metalloproteinase 9 and Osteopontin Interact to Support Synaptogenesis in the Olfactory Bulb after Mild Traumatic Brain Injury.
Olfactory receptor axons reinnervate the olfactory bulb (OB) after chemical or transection lesion. Diffuse brain injury damages the same axons, but the time course and regulators of OB reinnervation are unknown. Gelatinases (matrix metalloproteinase [MMP]2, MMP9) and their substrate osteopontin (OPN) are candidate mediators of synaptogenesis after central nervous system (CNS) insult, including olfactory axon damage. ⋯ Olfactory marker protein (OMP), used to identify injured olfactory axons, revealed persistent axon damage in the absence of MMP9. MMP9 KO ultrastructure at 21 days post-injury indicated that persistent OMP reduction was paired with delayed removal of degenerated axons. These results provide evidence that diffuse, concussive brain trauma induces a post-injury interaction between MMP9, OPN, and CD44, which mediates synaptic plasticity and reinnervation within the OB.