Journal of neurotrauma
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Journal of neurotrauma · Nov 2023
Repeated mild traumatic brain injury and JZL184 produce sex-specific increases in anxiety-like behavior and alcohol consumption in Wistar rats.
Alcohol use disorder (AUD) is highly comorbid with traumatic brain injury (TBI). Previously, using a lateral fluid percussion model (LFP) (an open-head injury model) to generate a single mild to moderate traumatic brain injury (TBI) we showed that TBI produces escalation in alcohol drinking, that alcohol exposure negatively impacts TBI outcomes, and that the endocannabinoid degradation inhibitor (JZL184) confers significant protection from behavioral and neuropathological outcomes in male rodents. In the present study, we used a weight drop model (a closed-head injury model) to produce repeated mild TBI (rmTBI; three TBIs separated by 24 hours) in male and female rats to examine the sex-specific effects on anxiety-like behavior and alcohol consumption, and whether systemic treatment with JZL184 would reverse TBI effects on those behaviors. ⋯ In Study 2, rmTBI once again increased alcohol consumption in female but not male rats, and repeated systemic treatment with JZL184 did not affect alcohol consumption. Also in Study 2, rmTBI increased anxiety-like behavior in males but not females and repeated systemic treatment with JZL184 produced an unexpected increase in anxiety-like behavior 6-8 days post-injury. In summary, rmTBI increased alcohol consumption in female rats, systemic JZL184 treatment did not alter alcohol consumption, and both rmTBI and systemic JZL184 treatment increased anxiety-like behavior 6-8 days post-injury in males but not females, highlighting robust sex differences in rmTBI effects.
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Journal of neurotrauma · Nov 2023
ReviewPEDIATRIC MODERATE AND SEVERE TRAUMATIC BRAIN INJURY: A SYSTEMATIC REVIEW OF CLINICAL PRACTICE GUIDELINE RECOMMENDATIONS.
Traumatic brain injury (TBI) is the leading cause of death and disability in children. Many clinical practice guidelines (CPGs) have addressed pediatric TBI in the last decade but significant variability in the use of these guidelines persists. Here, we systematically review CPGs recommendations for pediatric moderate-to-severe TBI, evaluate the quality of CPGs, synthesize the quality of evidence and strength of included recommendations, and identify knowledge gaps. ⋯ We identified gaps in evidence-based recommendations for red blood cell transfusion, plasma and platelet transfusion, thromboprophylaxis, surgical antimicrobial prophylaxis, early diagnosis of hypopituitarism, and mental health mangement. Many up-to-date CPGs are available, but there is a paucity of evidence to support recommendations, highlighting the urgent need for robust clinical research in this vulnerable population. Our results may be used by clinicians to identify recommendations based on the highest level of evidence, by healthcare administrators to inform guideline implementation in clinical settings, by researchers to identify areas where robust evidence is needed, and by guideline writing groups to inform the updating of existing guidelines or the development of new ones.
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Journal of neurotrauma · Nov 2023
ReviewIL-6 in traumatic brain injury: A Janus-faced player in damage and repair.
Traumatic brain injury (TBI) is a common and often devastating illness, with wide-ranging public health implications. In addition to the primary injury, victims of TBI are at risk for secondary neurological injury by numerous mechanisms. Current treatments are limited and do not target the profound immune response associated with injury. ⋯ In TBI, elevated IL-6 levels are associated with worse outcomes, but the role of IL-6 in response to injury is double-edged. IL-6 promotes neurogenesis and wound healing in animal models of TBI, but it may also contribute to disruptions in the BBB and the progression of cerebral edema. Here, we review IL-6 biology in the context of TBI, with an eye to clarifying its controversial role and understanding its potential as a target for modulating the immune response in this disease.
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Journal of neurotrauma · Nov 2023
Autoregulatory Management in Traumatic Brain Injury: the Role of Absolute PRx-Values and CPPopt Curve Shape.
The aim of this study was to investigate if the absolute pressure reactivity index (PRx) value influenced the association between cerebral perfusion pressure (CPP) and outcome and if the optimal CPP (CPPopt) curve shape influenced the association between deviation from CPPopt and outcome in traumatic brain injury (TBI). We included 383 TBI patients treated at the neurointensive care in Uppsala between 2008 and 2018 with at least 24 h of CPP data. To determine the influence of absolute PRx values on the association between absolute CPP and outcome, the percentage of monitoring time for combinations of CPP and PRx were correlated with outcome (Extended Glasgow Outcome Scale [GOS-E]) in a heatmap. ⋯ These regressions had similar area under receiver operating curve and were not superior to a similar regression when the CPPopt-target was replaced by the percentage of monitoring time within the traditional fixed CPP-targets 60 to 70 mm Hg. Individualized CPPopt-targets exhibited a comparable outcome association as traditional CPP targets and different definitions of the best CPPopt range based on the PRx value had a limited effect on the association between deviation from CPPopt and outcome. Since CPPopt could only be calculated during half of the time, an alternative approach would be to assess the absolute PRx to anticipate a safe CPP range.
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Journal of neurotrauma · Nov 2023
Validation of Military Occupational Specialty as a Proxy for Blast Exposure Using the Salisbury Blast Interview.
Abstract Evaluating large data sets precludes the ability to directly measure individual experiences, instead relying on proxies to infer certain constructs. Blast exposure is a construct of study currently in its infancy, resulting in diverse definitions and measurements across studies. The purpose of the present study was to validate military occupational specialty (MOS) as a proxy for blast exposure in combat veterans. ⋯ Sensitivity was low (36.46-51.14), indicating that MOS risk level was not a good predictor of the presence of these outcomes. Results demonstrate that high-risk MOSs will identify individuals with blast exposure and deployment TBI history whereas low-risk MOSs will capture a highly variable group. Accuracy of MOS categorization was not acceptable for diagnostic-level tests; however, results support its use as a screening measure for a history of exposure to blast, use in epidemiological studies, and considerations for military policy.