Journal of neurotrauma
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Journal of neurotrauma · Sep 2020
Neurons in Subcortical Oculomotor Regions are Vulnerable to Plasma Membrane Damage after Repetitive Diffuse Traumatic Brain Injury in Swine.
Oculomotor deficits, such as insufficiencies in accommodation, convergence, and saccades, are common following traumatic brain injury (TBI). Previous studies in patients with mild TBI attributed these deficits to insufficient activation of subcortical oculomotor nuclei, although the exact mechanism is unknown. A possible cause for neuronal dysfunction in these regions is biomechanically induced plasma membrane permeability. ⋯ Many permeabilized cells lost neuron-specific nuclear protein reactivity, although no neuronal loss occurred acutely after injury. Microglia contacted and appeared to begin phagocytosing permeabilized neurons in repetitively injured animals. These pathologies within oculomotor areas may mediate transient dysfunction and/or degeneration that may contribute to oculomotor deficits following diffuse TBI.
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Journal of neurotrauma · Sep 2020
Observational StudyA pilot study assessing the impact of rs174537 on circulating PUFAs and the inflammatory response in TBI patients.
Traumatic brain injury (TBI) is a leading cause of death and disability in persons under age 45. The hallmark secondary injury profile after TBI involves dynamic interactions between inflammatory and metabolic pathways including fatty acids. Omega-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) have been shown to provide neuroprotective benefits by minimizing neuroinflammation in rodents. ⋯ Specifically, TBI patients with GG genotype exhibited the highest plasma levels of DHA (1.33%) and interleukin-8 (121.5 ± 43.3 pg/mL), which were in turn associated with poorer outcomes. These data illustrate the impact of rs174537 on the post-TBI response. Further work is needed to ascertain how this genetic variant directly influences inflammation after trauma.
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Journal of neurotrauma · Sep 2020
Study design features associated with patient attrition in studies of traumatic brain injury - a systematic review.
Loss to follow-up or patient attrition is common in longitudinal studies of traumatic brain injury (TBI). Lack of understanding exists between the relation of study design and patient attrition. This review aimed to identify features of study design that are associated with attrition. ⋯ Conversely, two features were associated with a reduction in attrition: recruitment in an acute care setting defined as the ward or intensive care unit (OR: 0.58, 95% CI: 0.47-0.72) and a greater duration of time between injury and follow-up (OR: 0.93, 95% CI: 0.88-0.99). This review highlights design features that are associated with attrition and could be considered when planning for patient retention. Further work is needed to establish the mechanisms between the observed associations and potential remedies.
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Journal of neurotrauma · Sep 2020
Exploring Neuronal Vulnerability to Head Trauma using a Whole Exome Approach.
Brain injuries are associated with oxidative stress and a need to restore neuronal homeostasis. Mutations in ion channel genes, in particular CACNA1A, have been implicated in familial hemiplegic migraine (FHM) and in the development of concussion-related symptoms in response to trivial head trauma. The aim of this study was to explore the potential role of variants in other ion channel genes in the development of such responses. ⋯ Rare (MAF <0.001) or novel heterozygous variants in 7 ion channel genes were identified in 37.5% (6/16) of the cases (CACNA1I, CACNA1C, ATP10A, ATP7B, KCNAB1, KCNJ10, and SLC26A4), rare variants in neurotransmitter genes were found in 2 cases (GABRG1 and GRIK1), and rare variants in 3 ubiquitin-related genes identified in 4 cases (SQSTM1, TRIM2, and HECTD1). In this study, the largest proportion of potentially pathogenic variants in individuals with severe responses to minor head trauma were identified in genes previously implicated in migraine and seizure-related autosomal recessive neurological disorders. Together with results implicating variants in the hemiplegic migraine genes, CACNA1A and ATP1A2, in severe head trauma response, our results support a role for heterozygous deleterious mutations in genes implicated in neurological dysfunction and potentially increasing the risk of poor response to trivial head trauma.
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Journal of neurotrauma · Sep 2020
Repetitive Mild Traumatic Brain Injury and Transcription Factor Modulation.
The worldwide incidence of traumatic brain injury (TBI) is ∼0.5% per year and the frequency is significantly higher among military personnel and athletes. Repetitive TBIs are associated with military and athletic activities, and typically involve more severe consequences. The majority of TBIs are mild; however, these still can result in long-term cognitive deficits, and there is currently no effective treatment. tert-Butylhydroquinone (tBHQ) and pioglitazone can activate the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and peroxisome proliferator-activated receptor-gamma (PPAR-γ) transcription factors, respectively, and each has been shown to be neuroprotective in various model systems. ⋯ We found that memory performance was significantly reduced by the injuries, unless the TBIs were followed by the tBHQ and pioglitazone administrations. Certain genes; for example, growth hormone and osteopontin, were downregulated by the injury, and this was reversed by the treatment, whereas other genes; for example, a tumor necrosis factor receptor, were upregulated by the injury and restored if the post-injury treatment was administered. Analysis of gene expression levels affected by the injury and/or the treatment point to potential mechanisms that could be exploited therapeutically.