Journal of neurotrauma
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Journal of neurotrauma · Feb 2011
Therapeutic window analysis of the neuroprotective effects of cyclosporine A after traumatic brain injury.
Mitochondrial dysfunction plays a pivotal role in secondary cell death mechanisms following traumatic brain injury (TBI). Several reports have demonstrated that inhibition of the mitochondrial permeability transition pore with the immunosuppressant drug cyclosporine A (CsA) is efficacious. Accordingly, CsA is being moved forward into late-stage clinical trials for the treatment of moderate and severe TBI. ⋯ Treatment initiated at 1 h post-injury (∼68% decrease) was not significantly different than that seen at 3 h (∼46% decrease), but resulted in significantly greater cortical tissue sparing compared to CsA treatment initiated at least 4 h post-injury (28% decrease). Together these results illustrate the importance of initiating therapeutic interventions such as CsA as soon as possible following TBI, preferably within 4 h post-injury, to achieve the best possible neuroprotective effect. However, the drug appears to retain some protective efficacy even when initiated as late as 8 h post-injury.
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Journal of neurotrauma · Feb 2011
A survey of very-long-term outcomes after traumatic brain injury among members of a population-based incident cohort.
To assess quality of life and barriers to participation in vocational and community life for persons with traumatic brain injury (TBI) over the very-long term, a population-based cohort was identified in Olmsted County, Minnesota; 1623 individuals were identified as having experienced a confirmed TBI while a resident of Olmsted County, Minnesota, during the period from 1935-2000. A survey was sent to eligible individuals that included elements of standardized instruments addressing health status and disability, and questions that assessed issues important to successful social reintegration after TBI. Of 1623 eligible participants sent surveys, 605 responded (37% response rate). ⋯ Respondents with a longer time since injury were less likely to report any TBI-related problems. These results indicate that self-reported outcomes and adaptation to impairment-related limitations improve as the time since injury increases. These findings highlight the importance of providing coordinated medical rehabilitation and community-based support services to promote positive outcomes over the life span after TBI.
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Journal of neurotrauma · Feb 2011
A diffusion tensor imaging study on the white matter skeleton in individuals with sports-related concussion.
Recognizing and managing the effects of cerebral concussion is very challenging, given the discrete symptomatology. Most individuals with sports-related concussion will not score below 15 on the Glasgow Coma Scale, but will present with rapid onset of short-lived neurological impairment, demonstrating no structural changes on traditional magnetic resonance imaging (MRI) and computed tomography (CT) scans. The return-to-play decision is one of the most difficult responsibilities facing the physician, and so far this decision has been primarily based on neurological examination, symptom checklists, and neuropsychological (NP) testing. ⋯ Evaluation of fractional anisotropy (FA) and mean diffusivity (MD) of the WM skeleton using tract-based spatial statistics (TBSS) revealed a large cluster of significantly increased MD for concussed subjects in several WM fiber tracts in the left hemisphere, including parts of the inferior/superior longitudinal and fronto-occipital fasciculi, the retrolenticular part of the internal capsule, and posterior thalamic and acoustic radiations. Qualitative comparison of average FA and MD suggests that with increasing level of injury severity (ranging from sports-related concussion to severe traumatic brain injury), MD might be more sensitive at detecting mild injury, whereas FA captures more severe injuries. In conclusion, the TBSS analysis used to evaluate diffuse axonal injury of the WM skeleton seems sensitive enough to detect structural changes in sports-related concussion.
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Collaboration among investigators, centers, countries, and disciplines is essential to advancing the care for traumatic brain injury (TBI). It is thus important that we "speak the same language." Great variability, however, exists in data collection and coding of variables in TBI studies, confounding comparisons between and analysis across different studies. Randomized controlled trials can never address the many uncertainties concerning treatment approaches in TBI. ⋯ Endorsement of the recommendations has been obtained from many authoritative organizations. The development of CDEs for TBI should be viewed as a continuing process; as more experience is gained, refinement and amendments will be required. This proposed process of standardization will facilitate comparative effectiveness research and encourage high-quality meta-analysis of individual patient data.
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Journal of neurotrauma · Feb 2011
Comparative StudyDifferential effects of injury severity on cognition and cellular pathology after contusive brain trauma in the immature rat.
Although diffuse brain damage has been suggested to be the predominant predictor of neurological morbidity following closed head injury in infants and children, the presence of contusions also predicts long-term neurobehavioral dysfunction. Contusive brain trauma in the 17-day-old rat resulted in neurodegeneration and caspase activation in the cortex at 1 day, and in the thalamus at 3 days post-injury, and to a greater extent following a deeper impact. Cortical tissue loss in the 4-mm impact group was significantly greater than that in the 3-mm impact group (p < 0.05), and exhibited a time-dependent increase over the first 3 weeks post-injury. ⋯ Similarly, neurodegeneration and caspase activation in the hippocampus was restricted to the dentate gyrus and occurred to a similar extent in both injured groups. Only the 4-mm impact group exhibited learning deficits in the first week (p < 0.0001) that was sustained until the third week post-injury (p < 0.0001), while deficits in the 3-mm impact group were seen only at 3 weeks post-injury (p < 0.02). These observations demonstrate that increasing severity of injury in immature animals does not uniformly increase the extent of cellular damage, and that the progression of tissue damage and behavioral deficits varies as a function of injury severity.