Journal of neurotrauma
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Journal of neurotrauma · May 2012
Nandrolone normalizes determinants of muscle mass and fiber type after spinal cord injury.
Spinal cord injury (SCI) results in atrophy of skeletal muscle and changes from slow oxidative to fast glycolytic fibers, which may reflect reduced levels of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), increased myostatin signaling, or both. In animals, testosterone reduces loss of muscle fiber cross-sectional area and activity of enzymes of energy metabolism. To identify the molecular mechanisms behind the benefits of androgens on paralyzed muscle, male rats were spinal cord transected and treated for 8 weeks with vehicle, testosterone at a physiological replacement dose, or testosterone plus nandrolone, an anabolic steroid. ⋯ Thus, the findings demonstrate that following SCI, signaling through activin receptors and Smad2/3 is increased, and that androgens suppress activation of this signaling pathway. The findings also indicate that androgens upregulate PGC-1α in paralyzed muscle and promote its nuclear localization, but that these effects are insufficient to fully activate transcription of PGC-1α target genes. Furthermore, the transcription of these genes is not tightly coupled with their translation.
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Journal of neurotrauma · May 2012
Transplantation of mesenchymal stem cells promotes an alternative pathway of macrophage activation and functional recovery after spinal cord injury.
Mesenchymal stem cells (MSC) derived from bone marrow can potentially reduce the acute inflammatory response in spinal cord injury (SCI) and thus promote functional recovery. However, the precise mechanisms through which transplanted MSC attenuate inflammation after SCI are still unclear. The present study was designed to investigate the effects of MSC transplantation with a special focus on their effect on macrophage activation after SCI. ⋯ This was associated simultaneously with increased numbers of alternatively activated macrophages (M2 phenotype: arginase-1- or CD206-positive), and decreased numbers of classically activated macrophages (M1 phenotype: iNOS- or CD16/32-positive). These changes were associated with functional locomotion recovery in the MSC-transplanted group, which correlated with preserved axons, less scar tissue formation, and increased myelin sparing. Our results suggested that acute transplantation of MSC after SCI modified the inflammatory environment by shifting the macrophage phenotype from M1 to M2, and that this may reduce the effects of the inhibitory scar tissue in the subacute/chronic phase after injury to provide a permissive environment for axonal extension and functional recovery.
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Traumatic neuroma in continuity (NIC) results in profound neurological deficits, and its management poses the most challenging problem to peripheral nerve surgeons today. The absence of a clinically relevant experimental model continues to handicap our ability to investigate ways of better diagnosis and treatment for these disabling injuries. Various injury techniques were tested on Lewis rat sciatic nerves. ⋯ We have demonstrated histological features and poor functional recovery consistent with NIC formation in a rat model. The injury mechanism employed combines traction and compression forces akin to the physical forces at play in clinical nerve injuries. This model may serve as a tool to help diagnose this injury earlier and to develop intervention strategies to improve patient outcomes.
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Journal of neurotrauma · May 2012
ReviewAn overview of published research about the acute care and rehabilitation of traumatic brain injured and spinal cord injured patients.
Knowledge of the breadth, nature, and volume of traumatic brain injury (TBI) and spinal cord injury (SCI) research can aid in research planning. This study aimed to provide an overview of existing TBI and SCI research to inform identification of knowledge translation (KT), systematic review (SR), and primary research opportunities. Topics and relevant articles from three large neurotrauma evidence resources were synthesized: the Global Evidence Mapping (GEM) Initiative (129 topics and 1644 articles), the Acquired Brain Injury Evidence-Based Review (ERABI; 152 topics and 732 articles), and the Spinal Cord Injury Rehabilitation Evidence (SCIRE) Project (297 topics and 1650 articles). ⋯ Topics for which primary research may be needed included pharmacological therapies for neurological recovery post-TBI, and management of sleep-disordered breathing post-SCI. There was a larger volume of non-intervention (epidemiological) studies in SCI than in TBI. This comprehensive overview of TBI and SCI research can aid funding agencies, researchers, clinicians, and other stakeholders in prioritizing and planning TBI and SCI research.
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Journal of neurotrauma · May 2012
ReviewA systematic review of exercise training to promote locomotor recovery in animal models of spinal cord injury.
In the early 1980s experiments on spinalized cats showed that exercise training on the treadmill could enhance locomotor recovery after spinal cord injury (SCI). In this review, we summarize the evidence for the effectiveness of exercise training aimed at promoting locomotor recovery in animal models of SCI. We performed a systematic search of the literature using Medline, Web of Science, and Embase. ⋯ We recommend that future studies include control groups, randomize animals to groups, conduct blinded assessments, report the extent of the SCI lesion, and report sample size calculations. A small battery of objective assessment methods including assessment of over-ground stepping should also be developed and routinely employed. This would allow future meta-analyses of the effectiveness of exercise interventions on locomotor recovery.