Journal of neurotrauma
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Journal of neurotrauma · Nov 2024
Genetic Differences Modify Anesthetic Preconditioning of Traumatic Brain Injury in Drosophila.
Pre-clinical vertebrate models of traumatic brain injury (TBI) routinely use anesthetics for animal welfare; however, humans experience TBI without anesthetics. Therefore, translation of findings from vertebrate models to humans hinges on understanding how anesthetics influence cellular and molecular events that lead to secondary injuries following TBI. To investigate the effects of anesthetics on TBI outcomes, we used an invertebrate Drosophila melanogaster model to compare outcomes between animals exposed or not exposed to anesthetics prior to the same primary injury. ⋯ Finally, genome-wide association study analyses identified single-nucleotide polymorphisms in genes associated with isoflurane or sevoflurane preconditioning of TBI. Several of the genes, including the fly ortholog of mammalian Calcium Voltage-Gated Subunit Alpha1 D (CACNA1D), are highly expressed in neurons and are functionally linked to both anesthetics and TBI. These data indicate that anesthetic dose and genetic background should be considered when investigating effects of anesthetics in vertebrate TBI models, and they support use of the fly model for elucidating the mechanisms underlying anesthetic preconditioning of TBI.
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Journal of neurotrauma · Nov 2024
Evolution of Real-World Clinical Practice in Time to Surgery Following Thoracolumbar Spinal Cord Injury: An Observational Study of North American Trauma Centers from 2010 to 2020.
This study aims to estimate real-world clinical practice trends in time to surgery following thoracolumbar spinal cord injury (SCI) in trauma centers across North America over the last decade (2010-2020). A multi-center retrospective observational study was conducted using Trauma Quality Improvement Program data from 2010 to 2020. All surgically treated patients with thoracic and lumbar SCI were included. ⋯ Moreover, in a secondary analysis including 3270 patients with incomplete thoracolumbar SCI, a comparable significant annual reduction in time to surgery was demonstrated (IRR = 0.93, 95% CI: 0.91-0.94). This study provides real-world data on practice pattern trends with respect to time to spine surgery following traumatic thoracolumbar SCI. Over the years from 2010 to 2020, we found a significant reduction in time to surgery across trauma centers in North America.
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Journal of neurotrauma · Nov 2024
Time to Surgery Following Complete Cervical Spinal Cord Injury: Evolution of Clinical Practice Patterns Over a Decade from 2010 to 2020 Across North American Trauma Centers.
This study aims to quantify the change in time to surgery for treatment of complete traumatic cervical spinal cord injury (SCI) patients in American College of Surgeons accredited trauma centers across North America over the last decade (2010-2020). This multi-center retrospective observational cohort study used data from the Trauma Quality Improvement Program from 2010 to 2020. All surgically treated patients with complete traumatic cervical SCI were included. ⋯ A multi-variable adjusted model for time to surgery demonstrated a significant downward annual reduction of 5% in time to surgery between the years 2010 and 2020 (Incidence rate ratio = 0.95; 95% Confidence Interval: 0.93-0.96). This study provides compelling real-world based quantification of the change in time to surgical intervention following traumatic cervical SCI. A significant decreasing annual trend pertaining to surgical timing across trauma centers in North America over the past decade was demonstrated.
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Journal of neurotrauma · Nov 2024
Bradykinin 2 receptors (B2R) mediate long term neurocognitive deficits after experimental traumatic brain injury.
The kallikrein-kinin system is one of the first inflammatory pathways to be activated following traumatic brain injury (TBI) and has been shown to exacerbate brain edema formation in the acute phase through activation of bradykinin 2 receptors (B2R). However, the influence of B2R on chronic post-traumatic damage and outcome is unclear. In the current study, we assessed long-term effects of B2R-knockout (KO) after experimental TBI. ⋯ Scar formation and astrogliosis were unaffected, but B2R deficiency led to a gene-dose-dependent attenuation of microglial activation and a reduction of CD45+ cells 3 months after TBI in cortex (p = 0.0003) and hippocampus (p < 0.0001). These results suggest that chronic hippocampal neurodegeneration and subsequent cognitive impairment are mediated by prolonged neuroinflammation and B2R. Inhibition of B2R may therefore represent a novel strategy to reduce long-term neurocognitive deficits after TBI.