Journal of neurotrauma
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Journal of neurotrauma · Aug 2015
Neuronal DNA Methylation Profiling of Blast-related Traumatic Brain Injury (TBI).
Long-term molecular changes in the brain resulting from blast exposure may be mediated by epigenetic changes, such as deoxyribonucleic acid (DNA) methylation, that regulate gene expression. Aberrant regulation of gene expression is associated with behavioral abnormalities, where DNA methylation bridges environmental signals to sustained changes in gene expression. We assessed DNA methylation changes in the brains of rats exposed to three 74.5 kPa blast overpressure events, conditions that have been associated with long-term anxiogenic manifestations weeks or months following the initial exposures. ⋯ Functional validation via gene expression analysis of 30 differentially methylated neuronal and glial genes showed a 1.2 fold change in gene expression of the serotonin N-acetyltransferase gene (Aanat) in blast animals (p<0.05). These data provide the first genome-based evidence for changes in DNA methylation induced in response to multiple blast overpressure exposures. In particular, increased methylation and decreased gene expression were observed in the Aanat gene, which is involved in converting serotonin to the circadian hormone melatonin and is implicated in sleep disturbance and depression associated with traumatic brain injury.
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Estrogen plays an important role as a neuroprotector in the central nervous system (CNS), directly interacting with neurons and regulating physiological properties of non-neuronal cells. Here we evaluated estrogen sulfate (E2-SO4) for traumatic brain injury (TBI) using a Sprague-Dawley rat model. TBI was induced via lateral fluid percussion (LFP) at 24 h after craniectomy. ⋯ The edema size in the brains of the E2-SO4 treated group was also significantly smaller than that of vehicle-treated group at 1 day after E2-SO4 injection (p=0.04), and cerebral glycolysis of injured region was also increased significantly during the same time period (p=0.04). However, E2-SO4 treatment did not affect DAI (p>0.05). These findings demonstrated the potential benefits of E2-SO4 in TBI.
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Neurogenic pulmonary edema (NPE) is a life-threatening complication of central nervous system (CNS) injuries. This review summarizes current knowledge about NPE etiology and pathophysiology with an emphasis on its experimental models, including our spinal cord compression model. NPE may develop as a result of activation of specific CNS trigger zones located in the brainstem, leading to a rapid sympathetic discharge, rise in systemic blood pressure, baroreflex-induced bradycardia, and enhanced venous return resulting in pulmonary vascular congestion characterized by interstitial edema, intra-alveolar accumulation of transudate, and intra-alveolar hemorrhages. ⋯ Sympathetic hyperactivity is based on the major activation of either ascending spinal pathways by spinal cord injury or NPE trigger zones by increased intracranial pressure. Attenuation of sympathetic nerve activity or abolition of reflex bradycardia completely prevent NPE development in our experimental model. Suggestions for future research into NPE pathogenesis as well as therapeutic potential of particular drugs and interventions are discussed.
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Journal of neurotrauma · Aug 2015
Comment LetterLetter to the editor. Commentary regarding the recent publication by Tabarow et al, Functional regeneration of supraspinal connections in a patient with transected spinal cord following transplantation of bulbar olfactory ensheathing cells with peripheral nerve bridging.
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Journal of neurotrauma · Aug 2015
Clinical TrialEffect of Mild Cold Exposure on Cognition in Persons with Tetraplegia.
Persons with a cervical spinal cord injury (SCI) have impaired thermoregulatory mechanisms secondary to interrupted of motor, sensory, and sympathetic pathways. In this study, our primary aim was to determine the effect of cool temperature exposure on core body temperature (Tcore) and cognitive performance in persons with tetraplegia. Seven men with chronic tetraplegia (C3-C7, American Spinal Injury Association Impairment Scale [AIS] A-C) and seven able-bodied controls were exposed to 27°C temperature at baseline (BL) before being exposed to 18°C for ≤120 min (Cool Challenge). Rectal temperature (Tcore), distal skin temperatures (Tskavg), microvascular skin perfusion (LDFavg), and systolic blood pressure (SBP) were measured. Cognitive performance was assessed using Delayed Recall, Stroop Interference tests at the end of BL and Cool Challenge. After Cool Challenge, Tcore decreased -1.2±0.12°C (p<0.0001) in tetraplegics after an average of 109±15.9 min with no change in controls after 120 min. Tskavg declined in both groups, but decline was less in tetraplegics than in controls (-8.6±5.8% vs. -31.6±7.9%, respectively; p<0.0001). LDFavg declined only in controls (-72±17.9%; p<0.001). Plasma norepinephrine levels differed after Cool Challenge (tetraplegics vs. ⋯ 86±62 pg/mL vs. 832±431 pg/mL, respectively; p<0.01). SBP increased from BL to Cool Challenge only in controls (123±16 mm Hg to 149±17 mm Hg, respectively; p<0.01). Delayed Recall and Stroop Interference scores both declined in tetraplegics (-55±47.4%; p<0.05 and -3.9±3.8%; p<0.05, respectively), but not in controls. We conclude that persons with tetraplegia lack adequate thermoregulatory mechanisms to prevent downward drift in Tcore on exposure to cool temperatures. This decline in Tcore was associated with deterioration of working memory and executive function.