Journal of neurotrauma
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Journal of neurotrauma · Feb 2017
Neuropsychiatric symptom modeling in male and female C57BL/6J mice following experimental traumatic brain injury.
Psychiatric symptoms such as anxiety and depression are frequent and persistent complaints following traumatic brain injury (TBI). Modeling these symptoms in animal models of TBI affords the opportunity to determine mechanisms underlying behavioral pathologies and to test potential therapeutic agents. However, testing these symptoms in animal models of TBI has yielded inconsistent results. ⋯ Increased levels of activity were also measured in female mice and injured mice in these tests, and conclusions regarding anxiety should be taken with caution when experimental manipulations induce changes in baseline activity. These results underscore the irreconcilability of results from studies attempting to model TBI-induced neuropsychiatric symptoms. Changes in injury models or better attempts to replicate the clinical syndrome may improve the translational applicability of rodent models of TBI-induced anxiety and depression.
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Journal of neurotrauma · Feb 2017
ReviewTranslational Relevance of Swine Models of Spinal Cord Injury.
Spinal cord injury (SCI) is a physically and psychologically devastating clinical condition. The typical treatment regimens of decompressive surgery and rehabilitation therapy still leave many patients with permanent disability. The development of new therapies and devices can be accelerated if relevant translational animal models are more effectively used in pre-clinical stages. ⋯ Several spine injury models have recently been developed for swine and are beginning to be used to evaluate new therapies. Swine models of SCI offer tremendous advantages for efficient translation of pre-clinical discoveries and the development of new therapies and devices. Future swine models will also be enhanced by advances in gene-editing technology to further elucidate the complex pathophysiology associated with SCI and provide a means to engineer specific spinal pathologies.
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Journal of neurotrauma · Feb 2017
High-Mobility Group Box 1 (HMGB1) is Elevated Systemically in Persons with Acute or Chronic Traumatic Spinal Cord Injury.
Inflammation in traumatic spinal cord injury (SCI) has been proposed to promote damage acutely and oppose functional recovery chronically. However, we do not yet understand the signals that initiate or prolong inflammation in persons with SCI. High-Mobility Group Box 1 (HMGB1) is a potent systemic inflammatory cytokine-or damage-associated molecular pattern molecule (DAMP)-studied in a variety of clinical settings. ⋯ In persons with acute SCI, average HMGB1 levels were significantly elevated within 0-3 days post-injury (6.00 ± 1.8 ng/mL, mean ± standard error of the mean [SEM]) or 4-7 (6.26 ± 1.3 ng/mL, mean ± SEM), compared with controls (1.26 ± 0.24 ng/mL, mean ± SEM; p ≤ 0.001 and p ≤ 0.01, respectively). In persons with chronic SCI who were injured for 15 ± 1.5 years (mean ± SEM), HMGB1 also was significantly elevated, compared with uninjured persons (3.7 ± 0.69 vs. 1.26 ± 0.24 ng/mL, mean ± SEM; p ≤ 0.0001). Together, these data suggest that HMGB1 may be a common, early, and persistent danger signal promoting inflammation in individuals with SCI.
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Journal of neurotrauma · Feb 2017
Inter-rater Reliability of the International Standards to Document Remaining Autonomic Function following Spinal Cord Injury (ISAFSCI).
The autonomic nervous system can be profoundly affected after spinal cord injury (SCI). Despite its importance to quality of life, autonomic function is rarely systematically assessed in the clinical setting. The International Standards to Document Remaining Autonomic Function after Spinal Cord Injury (ISAFSCI) is an assessment designed to determine which autonomic functions are intact, impaired, or lost after SCI. ⋯ Inter-rater reliability within the general autonomic component was moderate with kappa values ranging 0.41-0.6 (p < 0.05). Within the Lower Urinary Tract, Bowel, and Sexual Function component, agreement was good-strong with weighted kappa values 0.62-0.88 (p < 0.05). Given the results, we conclude that the ISAFSCI can be considered to have at least moderate and up to strong inter-rater reliability, especially in the bladder, bowel, and sexual function component of the assessment.
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Journal of neurotrauma · Feb 2017
Clinical Trial Observational StudyCerebrospinal Fluid Biomarkers to Stratify Injury Severity and Predict Outcome in Human Traumatic Spinal Cord Injury.
Neurologic impairment after spinal cord injury (SCI) is currently measured and classified by functional examination. Biological markers that objectively classify injury severity and predict outcome would greatly facilitate efforts to evaluate acute SCI therapies. The purpose of this study was to determine how well inflammatory and structural proteins within the cerebrospinal fluid (CSF) of acute traumatic SCI patients predicted American Spinal Injury Association Impairment Scale (AIS) grade conversion and motor score improvement over 6 months. ⋯ Motor score improvement also was strongly correlated with the 24-h post-injury CSF levels of all six biomarkers. The analysis of CSF can provide valuable biological information about injury severity and recovery potential after acute SCI. Such biological markers may be valuable tools for stratifying individuals in acute clinical trials where variability in spontaneous recovery requires large recruitment cohorts for sufficient power.