Journal of neurotrauma
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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
Clinical TrialTraining in Goal-Oriented Attention Self-Regulation Improves Executive Functioning in Veterans with Chronic Traumatic Brain Injury.
Deficits in executive control functions are some of the most common and disabling consequences of both military and civilian brain injury. However, effective interventions are scant. The goal of this study was to assess whether cognitive rehabilitation training that was successfully applied in chronic civilian brain injury would be effective for military veterans with traumatic brain injury (TBI). ⋯ Training in attentional self-regulation applied to participant-defined goals may improve cognitive functioning in veterans with chronic TBI. Attention regulation training may not only impact executive control functioning in real-world complex tasks, but also may improve emotional regulation and functioning. Implications for treatment of veterans with TBI are discussed.
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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
The Moderating Effect of the Ankyrin Repeat and Kinase Domain Containing One Gene on the Association of Family Environment with Longitudinal Executive Function following Traumatic Brain Injury in Early Childhood: A Preliminary Study.
This study examined whether the ankyrin repeat and kinase domain containing 1 gene (ANKK1) C/T single-nucleotide polymorphism (SNP) rs1800497 moderated the association of family environment with long-term executive function (EF) following traumatic injury in early childhood. Caregivers of children with traumatic brain injury (TBI) and children with orthopedic injury completed the Behavior Rating Inventory of Executive Function (BRIEF) at post-injury visits. DNA was collected to identify the rs1800497 genotype in the ANKK1 gene. ⋯ Post hoc analyses found that carriers of the risk allele had significantly poorer EF compared with non-carriers only when they were from more advantaged environments. These results suggest a gene-environment interaction involving the ANKK1 gene as a predictor of EF in a pediatric injury population. The findings highlight the importance of considering environmental influences in future genetic studies on recovery following TBI and other traumatic injuries in childhood.
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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.