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
Activity-dependent increase in neurotrophic factors is associated with an enhanced modulation of spinal reflexes after spinal cord injury.
Activity-based therapies such as passive bicycling and step-training on a treadmill contribute to motor recovery after spinal cord injury (SCI), leading to a greater number of steps performed, improved gait kinematics, recovery of phase-dependent modulation of spinal reflexes, and prevention of decrease in muscle mass. Both tasks consist of alternating movements that rhythmically stretch and shorten hindlimb muscles. However, the paralyzed hindlimbs are passively moved by a motorized apparatus during bike-training, whereas locomotor movements during step-training are generated by spinal networks triggered by afferent feedback. ⋯ The animals were sacrificed and the spinal cords were harvested for Western blot analysis of the expression of neurotrophic factors in the lumbar spinal cord. We provide evidence that bike- and step-training significantly increase the levels of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and NT-4 in the lumbar enlargement of SCI rats, whereas only step-training increased glial cell-derived neurotrophic factor (GDNF) levels. An increase in neurotrophic factor protein levels that positively correlated with the recovery of H-reflex frequency-dependent depression suggests a role for neurotrophic factors in reflex normalization.
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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.