Journal of neurotrauma
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Journal of neurotrauma · Apr 2019
Systemic Estrone Production and Injury-Induced Sex Hormone Steroidogenesis after Severe Traumatic Brain Injury: A Prognostic Indicator of Traumatic Brain Injury-Related Mortality.
Extensive pre-clinical studies suggest that sex steroids are neuroprotective in experimental traumatic brain injury (TBI). However, clinical trials involving sex hormone administration have not shown beneficial results, and our observational cohort studies show systemic estradiol (E2) production to be associated with adverse outcomes. Systemic E2 is produced via aromatization of testosterone (T) or reduction of estrone (E1). ⋯ Structural equation models show that early serum E2 production is largely T independent, occurring predominantly through E1 metabolism. Acute serum E1 functions as a mortality marker for TBI through aromatase-dependent E1 production and T-independent E2 production. Further work should evaluate risk factors for high E2 production and how systemic E2 and its key intermediate E1 contribute to the extracerebral consequences of severe TBI.
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Journal of neurotrauma · Apr 2019
Transcallosal Fiber Disruption and its Relationship with Corresponding Gray Matter Alteration in Patients with Diffuse Axonal Injury.
Diffuse axonal injury (DAI) is characterized by diffuse white matter (WM) disruption caused by shearing forces acting on the brain. Cortical atrophy can be accompanied by WM disruption, which is assumed to reflect the loss of neuron cell bodies in gray matter (GM) regions adjacent to disrupted WM. It remains unclear whether WM disruption leads to regional GM alteration in DAI. ⋯ Among these regions, GM volume was reduced in 19 of 32 regions. There were no significant correlations between WM disruption in which abnormal connectivity was identified and the corresponding GM alterations. These results suggest that GM pathology is, at least in part, independent of the corresponding WM damage in DAI.
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Journal of neurotrauma · Apr 2019
Cerebral Oxygenation in Traumatic Brain Injury: Can a Non-Invasive Frequency Domain Near-Infrared Spectroscopy Device Detect Changes in Brain Tissue Oxygen Tension as Well as the Established Invasive Monitor?
The cost and highly invasive nature of brain monitoring modality in traumatic brain injury patients currently restrict its utility to specialist neurological intensive care settings. We aim to test the abilities of a frequency domain near-infrared spectroscopy (FD-NIRS) device in predicting changes in invasively measured brain tissue oxygen tension. Individuals admitted to a United Kingdom specialist major trauma center were contemporaneously monitored with an FD-NIRS device and invasively measured brain tissue oxygen tension probe. ⋯ Moderate hypoxic episodes were detected in seven individuals with similar predictive performance (AUROC 0.576-0.905). A variable performance in the predictive powers of this FD-NIRS device to detect changes in brain tissue oxygen was demonstrated. Consequently, this enhanced NIRS technology has not demonstrated sufficient ability to replace the established invasive measurement.
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Journal of neurotrauma · Apr 2019
KIAA0319 Genotype Predicts the Number of Past Concussions in a Division I Football Team: A Pilot Study.
This candidate gene study evaluated the relationship of a past history of concussion with single nucleotide polymorphisms (SNPs) in nine genes in a small cohort (N = 87) of a nationally ranked Division I football team. Genes and SNPs studied were selected based on their published connection to brain injury and brain development, as well as impulsivity. ⋯ The KIAA0319 results raise the hypothesis that having the CT or TT genotype of KIAA0319 may be predictive of a lower incidence of previously diagnosed concussion. This finding raises a number of hypotheses for future pre-clinical research, particularly whether alterations in neural organization related to KIAA0319 rs4504469 lead to reduced susceptibility for lasting head trauma, or greater resilience in the face of repeated subconcussive injury.
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Journal of neurotrauma · Apr 2019
Microglial Calcium Release-Activated Calcium Channel Inhibition Improves Outcome from Experimental Traumatic Brain Injury and Microglia-Induced Neuronal Death.
Store-operated Ca2+ entry (SOCE) mediated by calcium release-activated calcium (CRAC) channels contributes to calcium signaling. The resulting intracellular calcium increases activate calcineurin, which in turn activates immune transcription factor nuclear factor of activated T cells (NFAT). Microglia contain CRAC channels, but little is known whether these channels play a role in acute brain insults. ⋯ Male C57/BL6 mice exposed to experimental brain trauma and treated with CM-EX-137 had decreased lesion size, brain hemorrhage, and improved neurological deficits with decreased microglial activation, iNOS and Orai1 and STIM1 levels. We suggest a novel anti-inflammatory approach for managing acute brain injury. Our observations also shed light on new calcium signaling pathways not described previously in brain injury models.