Musculoskeletal Plasticity after Spinal Cord Injury

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 DESCRIPTION (provided by applicant): Patients with spinal cord injury (SCI) experience metabolic syndrome, diabetes, obesity, pressure ulcers, and cardiovascular disease at far greater rates than the general population. A rehabilitation method to prevent or reverse the systemic metabolic consequences of SCI is a pressing need. The purpose of this study is to determine the dose of muscle activity that can enhance an oxidative muscle phenotype, and improve clinical markers of metabolic and bone turnover health in patients with acute SCI. The long-term goal of this research is to develop exercise-based interventions to prevent secondary health conditions such as diabetes and to ultimately protect health-related quality of life (HRQOL). Specific Aim 1: To compare changes in skeletal muscle gene regulation in individuals with acute SCI who receive high muscle force standing (HS), low muscle force standing (LS), passive standing (PS), or usual care - (no stimulation and no standing, NS) for 16 weeks. We hypothesize that mRNA expression for metabolic transcription factors and for genes regulating glycolysis, fatty acid oxidation, tricarboxylic acid cycle, oxidative phosphorylation, and mitochondrial remodeling will support that HS and LS instigate a greater shift toward an oxidative muscle phenotype than PS or NS. A novel finding will be that LS is a powerful regulator of oxidative pathways in skeletal muscle. Specific Aim 2: To compare changes in systemic markers of metabolic health and bone turnover in individuals with SCI who receive HS, LS, PS, or NS for 16 weeks. We hypothesize that HS and LS will demonstrate lower glucose/insulin levels and greater glucagon suppression during oral glucose challenge compared to PS and NS. HS and LS will also demonstrate lower HOMA scores, hemoglobin A1c, fibroblast growth factor-21 (FGF21), and glucagon-like peptide 1 (GLP-1). LS will be an effective regulator of systemic markers of metabolism. We also hypothesize that HS will demonstrate higher serum levels of osteocalcin, lower levels of type 1 collagen C-telopeptide (CTX), and lower levels of sclerostin than all other groups (HS>LS>PS>NS), indicating an anti-catabolic effect on bone. As a secondary aim, we will measure secondary health conditions (SHCs), HRQOL, and cost effectiveness. We expect that the HS, LS, and PS groups will all show a trend for improved SHCs and HRQOL compared to usual care. We also expect to see an association between metabolic improvement and improved perception of HRQOL. These observations will support that this intervention has strong feasibility for future clinical translaion.