Journal of neurotrauma
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Journal of neurotrauma · Apr 2014
Assessment of an Experimental Rodent Model of Pediatric Mild Traumatic Brain Injury.
Childhood is one the highest risk periods for experiencing a mild traumatic brain injury (mTBI) from sports-related concussions, motor vehicle accidents, and falls. In addition, many children experience lingering symptomology (post-concussion syndrome) from these closed head injuries. Although the negative sequel of mTBI has been described, a clinically reliable animal model of mild pediatric brain injury has not. ⋯ Juvenile rats who experienced a single mTBI displayed significant motor/balance impairments when tested on the beam walking task and in the open field, as well as deficits of executive functioning as measured with the novel context mismatch task and the probe trial of the Morris water task. In addition, both male and female rats showed depression-like behavior in the forced swim task, with male rats also exhibiting decreased anxiety-related behaviors in the elevated plus maze. The results from this study suggest that the modified weight-drop technique induces a clinically relevant behavioral phenotype in juvenile rats, and may provide researchers with a reliable animal model of mTBI/concussion from which clinical therapeutic strategies could be developed.
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Journal of neurotrauma · Apr 2014
Prevalence of and risk factors for poor functioning after isolated mild traumatic brain injury in children.
This study aimed to determine the prevalence and predictors of poor 3 and 12 month quality of life outcomes in a cohort of pediatric patients with isolated mild TBI. We conducted a prospective cohort study of children and adolescents <18 years of age treated for an isolated mild TBI, defined as "no radiographically apparent intracranial injury" or "an isolated skull fracture, and no other clinically significant non-brain injuries." The main outcome measure was the change in quality of life from baseline at 3 and 12 months following injury, as measured by the Pediatric Quality of Life index (PedsQL). ⋯ Significant predictors of poor functioning included less parental education, Hispanic ethnicity (at 3 months following injury, but not at 12 months); low household income (at 3 and 12 months), and Medicaid insurance (at 12 months only). Children and adolescents sustaining a mild TBI who are socioeconomically disadvantaged may require additional intervention to mitigate the effects of mild TBI on their functioning.
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Journal of neurotrauma · Apr 2014
Post-acute Brain Injury Urinary Signature: A New Resource for Molecular Diagnostics.
Heterogeneity within brain injury presents a challenge to the development of informative molecular diagnostics. Recent studies show progress, particularly in cerebrospinal fluid, with biomarker assays targeting one or a few structural proteins. Protein-based assays in peripheral fluids, however, have been more challenging to develop, in part because of restricted and intermittent barrier access. ⋯ Identified peptide constituents were enriched for outgrowth and guidance, extracellular matrix, and post-synaptic density proteins, which were reflective of ongoing post-acute neuroplastic processes demonstrating pathobiological relevance. Taken together, these findings support further development of diagnostics based on brain injury urinary signatures using either combinatorial quantitative models or pattern-recognition methods. Particularly, these findings espouse assay development to address unmet diagnostic and theragnostic needs in brain injury rehabilitative medicine.
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Journal of neurotrauma · Apr 2014
CSF Cortisol and Progesterone Profiles and Outcomes Prognostication after Severe TBI.
Despite significant advances in the management of head trauma, there remains a lack of pharmacological treatment options for traumatic brain injury (TBI). While progesterone clinical trials have shown promise, corticosteroid trials have failed. The purpose of this study was to (1) characterize endogenous cerebrospinal fluid (CSF) progesterone and cortisol levels after TBI, (2) determine relationships between CSF and serum profiles, and (3) assess the utility of these hormones as predictors of long-term outcomes. ⋯ As a precursor to cortisol, progesterone mediated these effects. Serum and CSF levels for both cortisol and progesterone were strongly correlated after TBI relative to controls, possibly because of blood-brain barrier disruption. Also, differentially impaired hormone transport and metabolism mechanisms after TBI, potential de novo synthesis of steroids within the brain, and the complex interplay of cortisol and pro-inflammatory cytokines may explain these acute hormone profiles and, when taken together, may help shed light on why corticosteroid trials have previously failed and why progesterone treatment after TBI may be beneficial.
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Journal of neurotrauma · Apr 2014
Temporal course of changes in gene expression suggests a cytokine-related mechanism for long-term hippocampal alteration after controlled cortical impact.
Mild traumatic brain injury (mTBI) often has long-term effects on cognitive function and social behavior. Altered gene expression may be predictive of long-term psychological effects of mTBI, even when acute clinical effects are minimal or transient. Controlled cortical impact (CCI), which causes concussive, but nonpenetrant, trauma to underlying (non-cortical) brain, resulting in persistent changes in hippocampal synaptic function, was used as a model of mTBI. ⋯ Ccl2 and Ccl7 transcripts were up-regulated within 24 h after CCI, and their elevation subsided within 1 week of injury. Other transcriptional changes occurred later and were more stable, some persisting for at least 1 month, suggesting that short-term inflammatory responses trigger longer-term alteration in the expression of genes previously associated with injury, aging, and neuronal function in the brain. These transcriptional responses to mTBI may underlie long-term changes in excitatory and inhibitory neuronal imbalance in hippocampus, leading to long-term behavioral consequences of mTBI.