Journal of neurotrauma
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Journal of neurotrauma · Dec 2018
Neutralization of Interleukin-1β following Diffuse Traumatic Brain Injury in the Mouse Attenuates the Loss of Mature Oligodendrocytes.
Traumatic brain injury (TBI) commonly results in injury to the components of the white matter tracts, causing post-injury cognitive deficits. The myelin-producing oligodendrocytes (OLs) are vulnerable to TBI, although may potentially be replaced by proliferating oligodendrocyte progenitor cells (OPCs). The cytokine interleukin-1β (IL-1β) is a key mediator of the complex inflammatory response, and when neutralized in experimental TBI, behavioral outcome was improved. ⋯ The proliferation of OPCs in brain-injured animals was not altered, however. Our data suggest that IL-1β is involved in the TBI-induced loss of OLs and early microglia/macrophage activation, although not the OPC proliferation. Attenuated oligodendrocyte cell loss may contribute to the improved behavioral outcome observed by IL-1β neutralization in this mouse model of diffuse TBI.
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Journal of neurotrauma · Dec 2018
Efficacy and Harms of Pharmacological Interventions for Neurobehavioral Symptoms in Post-Traumatic Amnesia after Traumatic Brain Injury: A Systematic Review.
Many individuals in post-traumatic amnesia (PTA) following traumatic brain injury (TBI) experience neurobehavioral symptoms (NBS) in addition to disorientation and amnesia. These symptoms are associated with low rehabilitation engagement, self-inflicted harm, and risk of violence. The aim of this systematic review was to evaluate the efficacy and harms of pharmacological interventions for NBS in PTA following TBI in adults. ⋯ Less rigorous studies reported reduced NBS in patients administered haloperidol, ziprasidone, carbamazepine, amitriptyline, desipramine, and varied neuroleptics. There is a paucity of well-designed, adequately powered and controlled studies of pharmacological interventions for NBS in PTA. More research is needed to provide evidence-based treatment recommendations and improve care.
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Journal of neurotrauma · Dec 2018
Lithium Improves Dopamine Neurotransmission and Increases Dopaminergic Protein Abundance in the Striatum after Traumatic Brain Injury.
Experimental models of traumatic brain injury (TBI) recapitulate secondary injury sequela and cognitive dysfunction reported in patients afflicted with a TBI. Impairments in neurotransmission are reported in multiple brain regions in the weeks following experimental TBI and may contribute to behavioral dysfunction. Formation of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex is an important mechanism for neurotransmitter exocytosis. ⋯ We provide novel evidence that CCI reduces SNARE protein and SNARE complex abundance in the striatum at 1 week post-injury. Lithium administration improved evoked dopamine release and increased the abundance of α-synuclein, D2 receptor, and phosphorylated tyrosine hydroxylase in striatal synaptosomes post-injury. These findings show that lithium treatment attenuated dopamine neurotransmission deficits and increased the abundance of synaptic proteins important for dopamine signaling after TBI.
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Journal of neurotrauma · Dec 2018
GuidelinePreclinical Testing of Therapies for Traumatic Brain Injury.
Despite the large number of promising neuroprotective agents identified in experimental traumatic brain injury (TBI) studies, none has yet shown meaningful improvements in long-term outcome in clinical trials. To develop recommendations and guidelines for pre-clinical testing of pharmacological or biological therapies for TBI, the Moody Project for Translational Traumatic Brain Injury Research hosted a symposium attended by investigators with extensive experience in pre-clinical TBI testing. The symposium participants discussed issues related to pre-clinical TBI testing including experimental models, therapy and outcome selection, study design, data analysis, and dissemination. ⋯ Symposium participants agreed that the publication of negative results would reduce costly and unnecessary duplication of unsuccessful experiments. Although some of the recommendations are more relevant to multi-center, multi-investigator collaborations, most are applicable to pre-clinical therapy testing in general. The goal of these consensus guidelines is to increase the likelihood that therapies that improve outcomes in pre-clinical studies will also improve outcomes in TBI patients.
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Journal of neurotrauma · Dec 2018
Validation of Intracranial Pressure-Derived Cerebrovascular Reactivity Indices against the Lower Limit of Autoregulation, Part II: Experimental Model of Arterial Hypotension.
The aim of this work was to explore the relationship between intracranial pressure (ICP)-derived indices of cerebrovascular reactivity and the lower limit of autoregulation (LLA) during arterial hypotension. We retrospectively reviewed recorded physiological data from piglets that underwent controlled hypotension. Hypotension was induced by inflation of a balloon catheter in the inferior vena cava. ⋯ CPP at clinically relevant thresholds for PRx, PAx, and RAC displayed weak associations with the LLA, indicating that thresholds defined in TBI may not apply to a model of arterial hypotension. ROC analysis indicated that PRx, PAx, and RAC predicted the LLA, with AUCs of: 0.806 (95% confidence interval [CI], 0.750-0.863; p < 0.0001), 0.726 (95% CI, 0.664-0.789; p < 0.0001), and 0.710 (95% CI, 0.646-0.775; p < 0.0001), respectively. Three ICP-derived continuous indices of cerebrovascular reactivity, PRx, PAx, and RAC, were validated against the LLA within this experimental model of arterial hypotension, with PRx being superior.