Methylprednisolone and acute spinal cord injury: an update of the randomized evidence.
ABSTRACT Randomized trials are widely recognized as providing the most reliable evidence for assessing efficacy and safety of therapeutic interventions. This evidence base is used to evaluate the current status of methylprednisolone (MPSS) in the early treatment of acute spinal cord injury.
Medline, CINAHL, and other specified databases were searched for MeSH headings "methylprednisolone and acute spinal cord injury." The Cochrane Library and an existing systematic review on the topic were also searched.
Five randomized controlled trials were identified that evaluated high-dose MPSS for acute spinal cord injury. Three trials by the NASCIS group were of high methodologic quality, and a Japanese and French trial of moderate to low, methodologic quality. Meta-analysis of the final result of three trials comparing 24-hour high-dose MPSS with placebo or no therapy indicates an average unilateral 4.1 motor function score improvement (95% confidence interval 0.6-7.6, P = 0.02) in patients treated with MPSS. This neurologic recovery is likely to be correlated with improved functional recovery in some patients. The safety of this regimen of MPSS is evident from the spinal cord injury trials and a systematic review of 51 surgical trials of high-dose MPSS.
High-dose MPSS given within 8 hours of acute spinal cord injury is a safe and modestly effective therapy that may result in important clinical recovery for some patients. Further trials are needed to identify superior pharmacologic therapies and to test drugs that may sequentially influence the postinjury cascade.
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ABSTRACT: The regenerative capacity of injured adult central nervous system (CNS) tissue is very limited. Specifically, traumatic spinal cord injury (SCI) leads to permanent loss of motor and sensory functions below the site of injury, as well as other detrimental complications. A potential regenerative strategy is stem cell transplantation; however, cell survival is typically less than 1%. To improve cell survival, stem cells can be delivered in a biomaterial matrix that provides an environment conducive to survival after transplantation. One major challenge in this approach is to define the biomaterial and cell strategies in vitro. To this end, we investigated both peptide-modification of gellan gum and olfactory ensheathing glia (OEG) on neural stem/progenitor cell (NSPC) fate. To enhance cell adhesion, the gellan gum (GG) was modified using Diels-Alder click chemistry with a fibronectin-derived synthetic peptide (GRGDS). Amino acid analysis demonstrated that approximately 300 nmol of GRGDS was immobilized to each mg of GG. The GG-GRGDS had a profound effect on NSPC morphology and proliferation, distinct from that of NSPCs in GG alone, demonstrating the importance of GRGDS for cell-GG interaction. To further enhance NSPC survival and outgrowth, they were cultured with OEG. Here NSPCs interacted extensively with OEG, demonstrating significantly greater survival and proliferation relative to monocultures of NSPCs. These results suggest that this co-culture strategy of NSPCs with OEG may have therapeutic benefit for SCI repair.Biomaterials 06/2012; 33(27):6345-54. · 8.31 Impact Factor
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ABSTRACT: There is strong evidence indicating that the social environment triggers changes to the psychological stress response and glucocorticoid receptor function. Considerable literature links the subsequent changes in stress resiliency to physical health. Here, converging evidence for the modulatory role of chronic psychological stress in the recovery process following spinal cord injury (SCI) is presented. Despite the considerable advances in SCI research, we are still unable to identify the causes of variability in patients' recovery following injury. We propose that individuals' past and present life experiences (in the form of stress exposure) may significantly modulate patients' outcome post-SCI. We propose a theoretical model to explain the negative impact of chronic psychological stress on physical and psychological recovery. The stress experienced in life prior to SCI and also as a result of the traumatic injury, could compromise glucocorticoid receptor sensitivity and function, and contribute to high levels of inflammation and apoptosis post-SCI, decreasing the tissue remaining at the injury site and undermining recovery of function. Both stress-induced glucocorticoid resistance and stress-induced epigenetic changes to the glucocorticoid receptor can modulate the nuclear factor-kappa B regulated inflammatory pathways and the Bcl-2 regulated apoptosis pathways. This model not only contributes to the theoretical understanding of the recovery process following injury, but also provides concrete testable hypotheses for future studies.Frontiers in Neurology 01/2014; 5:44.
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ABSTRACT: Spine stabilization upon spinal cord injury (SCI) is a standard procedure in clinical practice, but rarely employed in experimental models. Moreover, the application of biodegradable biomaterials for this would come as an advantage as it would eliminate the presence of a nondegradable prosthesis within the vertebral bone. Therefore, in the present work, we propose the use of a new biodegradable device specifically developed for spine stabilization in a rat model of SCI. A 3D scaffold based on a blend of starch with polycaprolactone was implanted, replacing delaminated vertebra, in male Wistar rats with a T8-T9 spinal hemisection. The impact of spinal stabilization on the locomotor behavior was then evaluated for a period of 12 weeks. Locomotor evaluation-assessed by Basso, Beatie, and Bresnahan test; rotarod; and open field analysis-revealed that injured rats subjected to spine stabilization significantly improved their motor performance, including higher coordination and rearing activity when compared with SCI rats without stabilization. Histological analysis further revealed that the presence of the scaffolds not only stabilized the area, but also simultaneously prevented the infiltration of the injury site by connective tissue. Overall, these results reveal that SCI stabilization using a biodegradable scaffold at the vertebral bone level leads to an improvement of the motor deficits and is a relevant element for the successful treatment of SCI.Tissue Engineering Part C Methods 07/2012; · 4.64 Impact Factor