Journal of neurotrauma
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Journal of neurotrauma · Jul 2020
Neuroinflammation Mediated by GMF Exacerbates Neuronal Injury in an in vitro Model of Traumatic Brain Injury.
Traumatic brain injury (TBI) is the primary cause of death and disability affecting over 10 million people in the industrialized world. TBI causes a wide spectrum of secondary molecular and cellular complications in the brain. However, the pathological events are still not yet fully understood. ⋯ In addition, injured WT cells showed increased levels of oxidation product 4-hydroxynonenal and 8-oxo-2'-deoxyguanosine compared with injured GMF-KO cells. Further, we found that injured WT cells showed a significantly increased expression of glial fibrillary acidic protein, ionized calcium binding adaptor molecule 1, and phosphorylated ezrin/radixin/moesin proteins, and reduced microtubule associated protein expression compared with injured GMF-KO cells after injury. Collectively, our results demonstrate that GMF exacerbates the oxidative stress-mediated neuroinflammation that could be brought about by TBI-induced astroglial activation.
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Journal of neurotrauma · Jul 2020
Pediatric traumatic brain injury causes long-term deficits in adult hippocampal neurogenesis and cognition.
Young children who have sustained severe traumatic brain injury (TBI) can suffer from debilitating neurocognitive deficits. Impairment of adult hippocampal neurogenesis is associated with cognitive deficits and depression. Very few studies have investigated the adult hippocampal neurogenesis after pediatric TBI. ⋯ We found that: 1) pediatric TBI caused significant deficits in hippocampal dependent cognitive functions; 2) the survival rates of adult-born neurons at both ipsilateral and contralateral hippocampus significantly decreased in the TBI group; 3) TBI induced ectopic migration of adult-born neurons at the dorsal dentate gyrus in both ipsilateral and contralateral hippocampus; 4) TBI increased astrogenesis in the hilus of the dentate gyrus; and 5) TBI results in abnormal microglial activation. In conclusion, pediatric TBI causes prolonged neuroinflammation and dysregulation of the adult hippocampal neurogenesis through young adulthood, which might be responsible for the cognitive deficits. Protection of adult hippocampal neurogenesis may potentially improve outcomes.
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Journal of neurotrauma · Jul 2020
Latent class analysis to classify injury severity in pediatric TBI.
Heterogeneity of injury severity among children with traumatic brain injury (TBI) classified by the Glasgow Coma Scale (GCS) makes comparisons across research cohorts, enrollment in clinical trials, and clinical predictions of outcomes difficult. The present study uses latent class analysis (LCA) to distinguish severity subgroups from a prospective cohort of 433 children 2.5-15 years of age with TBI who were recruited from two level 1 pediatric trauma centers. Indicator variables available within 48 h post-injury including emergency department (ED) GCS, hospital motor GCS, Abbreviated Injury Score (AIS), Rotterdam Score, hypotension in the ED, and pre-hospital loss of consciousness, intubation, seizures, and sedation were evaluated to define subgroups. ⋯ Differences in outcomes in relation to AIS were restricted to the most and less severely injured at both time points. This study distinguished four latent classes that are clinically meaningful, distinguished a more homogenous severe injury group, and separated children by 6-month functional outcomes better than GCS alone. Systematic reporting of these variables would allow comparisons across research cohorts, potentially improve clinical predictions, and increase sensitivity to treatment effects in clinical trials.
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Journal of neurotrauma · Jul 2020
Comparative StudyA Comparison of Methods for Classifying Persistent Post-concussive Symptoms in Children.
Pediatric mild traumatic brain injury (pmTBI) has received increased public scrutiny over the past decade, especially regarding children who experience persistent post-concussive symptoms (PPCS). However, several methods for defining PPCS exist in clinical and scientific literature, and even healthy children frequently exhibit non-specific, concussive-like symptoms. Inter-method agreement (six PPCS methods), observed misclassification rates, and other psychometric properties were examined in large cohorts of consecutively recruited adolescent patients with pmTBI (n = 162) 1 week and 4 months post-injury and in age/sex-matched healthy controls (HC; n = 117) at equivalent time intervals. ⋯ In conclusion, the self-reporting of symptom burden is only modestly reliable in typically developing adolescents over a 4-month period, with additional evidence for systematic bias in both adolescent and parental ratings. Significant variation existed for identifying pmTBI patients who had "recovered" (i.e., those who did not meet individual criteria for PPCS) from concussion across the six definitions, representing a considerable challenge for estimating the true incidence rate of PPCS in published literature. Although relatively straightforward to obtain, current findings question the utility of the most commonly used Simple Change scores for diagnosis of PPCS in clinical settings.
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Journal of neurotrauma · Jul 2020
Observational StudyUsing Variance to Explore the Diagnostic Utility of Baseline Concussion Testing.
The Graded Symptom Checklist (GSC), Standardized Assessment of Concussion (SAC), Balance Error Scoring System (BESS), and King-Devick Test (KDT) are considered important components of concussion assessment. Whether baseline testing improves the diagnostic utility of these tests remains unclear. We performed an observational cohort study to investigate the within-subject and between-subjects variability of these tests over repeated assessments during two football seasons to examine whether baseline testing reduces variability in test performance. ⋯ A small, but significant, practice effect was observed for the BESS and KDT tests. When athletes are evaluated during a football season for concussion using the GSC, SAC, and BESS, comparing their scores to baseline performance is likely no more beneficial than comparing them to normative population data for identifying neurological changes associated with concussion. For the KDT, comparison to baseline testing is likely beneficial because of significantly higher between-subjects variability.