Journal of neurotrauma
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Journal of neurotrauma · Jul 2020
Penetrating Traumatic Brain Injury Triggers Subacute Dysregulation of Cathepsin B Protein Levels Independently of Cysteine Protease Activity in Brain and Cerebral Spinal Fluid.
Cathepsin B (CatB), a lysosomal cysteine protease, is important to brain function and may have dual utility as a peripheral biomarker of moderate-severe traumatic brain injury (TBI). The present study determined levels of pro- and mature (mat) CatB protein as well as cysteine protease activity within the frontal cortex (FC; proximal injury site), hippocampus (HC; distal injury site), and cerebral spinal fluid (CSF) collected 1-7 days after craniotomy and penetrating ballistic-like brain injury (PBBI) in rats. Values were compared with naïve controls. ⋯ Notably, CatB levels were significantly higher in CSF collected within 3 days after TBI compared with non-TBI controls. Collectively, this work indicates that CatB and its cysteine protease activity may serve as collective molecular signatures of TBI progression that differentially vary within both proximal and distal brain regions. CatB and its protease activity may have utility as a surrogate, translational biomarker of acute-subacute TBI.
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Journal of neurotrauma · Jul 2020
Acute Effects of Sport-Related Concussion on Serum GFAP, UCH-L1, Total Tau, and Neurofilament Light Measured by a Multiplex Assay.
We prospectively evaluated serum concentrations of glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), total tau (T-Tau), and neurofilament light (NF-L) from collegiate athletes at baseline and acutely after sport-related concussion (SRC) using the Quanterix Neurology 4Plex "B" (N4PB) multiplex assay. Uninjured controls were matched on age, sex, race, sport, and concussion history. Clinical outcomes included acute symptom severity, balance, rapid automated naming, computerized cognitive testing, and recovery duration. ⋯ There were no associations between biomarker concentrations and clinical measurements post-SRC or recovery duration. These findings suggest that, using the multiplex assay, GFAP, T-Tau, and NF-L elevate from baseline acutely after SRC, and both GFAP and NF-L excellently distinguished concussed from control cases. Serum biomarker changes do not necessarily correspond with clinical measurements or recovery duration.
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Journal of neurotrauma · Jul 2020
Multicenter StudyRelationship between measures of cerebrovascular reactivity and intracranial lesion progression in acute TBI patients: a CENTER-TBI study.
Failure of cerebral autoregulation has been linked to unfavorable outcome after traumatic brain injury (TBI). Preliminary evidence from a small, retrospective, single-center analysis suggests that autoregulatory dysfunction may be associated with traumatic lesion expansion, particularly for pericontusional edema. The goal of this study was to further explore these associations using prospective, multi-center data from the Collaborative European Neurotrauma Effectiveness Research in TBI (CENTER-TBI) and to further explore the relationship between autoregulatory failure, lesion progression, and patient outcome. ⋯ Total hemorrhagic core and edema volumes on repeat CT were significantly larger in patients who were deceased at 6 months, and the amount of edema was greater in patients with an unfavourable outcome (Glasgow Outcome Scale-Extended 1-4). Our study suggests associations between autoregulatory failure, traumatic edema progression, and poor outcome. This is in keeping with findings from a single-center retrospective analysis, providing multi-center prospective data to support those results.
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Journal of neurotrauma · Jul 2020
The Cumulative Influence of Inflammatory Response Genetic Variation on Long-Term Neurobehavioral Outcomes following Pediatric Traumatic Brain Injury Relative to Orthopedic Injury: An Exploratory Polygenic Risk Score.
The addition of genetic factors to prognostic models of neurobehavioral recovery following pediatric traumatic brain injury (TBI) may account for unexplained heterogeneity in outcomes. The present study examined the cumulative influence of candidate genes involved in the inflammatory response on long-term neurobehavioral recovery in children with early childhood TBI relative to children with orthopedic injuries (OI). Participants were drawn from a prospective, longitudinal study evaluating outcomes of children who sustained TBI (n = 67) or OI (n = 68) between the ages of 3 and 7 years. ⋯ Higher inflammatory response PRS were associated with more executive dysfunction and behavior problems in children with TBI but not in children with OI. The cumulative influence of inflammatory response genes as measured by PRS explained additional variance in long-term neurobehavioral outcomes, over and above well-established predictors and single candidate SNPs tested individually. The results suggest that some of the unexplained heterogeneity in long-term neurobehavioral outcomes following pediatric TBI may be attributable to a child's genetic predisposition to a greater or lesser inflammatory response to TBI.
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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.