Novel Intervention to Influence Muscle Plasticity in Veterans with SCI

影响 SCI 退伍军人肌肉可塑性的新型干预措施

• 批准号: 8894382
• 负责人: RICHARD K. SHIELDS
• 金额: --
• 依托单位: IOWA CITY VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8894382
• 关键词: Actins; Address; Affect; Area; Atrophic; Bilateral; Biological Preservation; Biomechanics; Biopsy; Blood; Bone Density; C-reactive protein; Cardiovascular system; Caring; Catabolism; Chemosensitization; Chronic; Clinical Trials; Complications of Diabetes Mellitus; Degradation Pathway; Diabetes Mellitus; Dose; Down-Regulation; Electric Stimulation; Exercise; Fatigue; Femur; Fracture; Frequencies; Future; Gene Expression; Gene Expression Regulation; General Population; Genes; Goals; Health; Health system; Heart Diseases; Human; Hypertrophy; Image; Individual; Insulin; Interleukin-6; Intervention; Lead; Left; Leg; Life; Limb structure; Link; Lower Extremity; Magnetic Resonance Imaging; Maintenance; Messenger RNA; Metabolic; Metabolic Marker; Metabolic syndrome; Methods; Molecular; Monitor; Muscle; Muscle Contraction; Muscle Fibers; Muscle function; Muscular Atrophy; Musculoskeletal System; Myosin ATPase; Outcome; Outcomes Research; Paralysed; Pathway interactions; Performance; Persons; Pharmacologic Substance; Physiological; Property; Protein Biosynthesis; Proteins; Quality of life; Recruitment Activity; Rehabilitation therapy; Relative (related person); Research; Risk; Savings; Skeletal system; Societies; Spinal cord injury; Stimulus; Stress; Testing; Training; Translating; Troponin; Up-Regulation; Veterans; activating transcription factor 4; bone; bone loss; bone stress; cohort; cost; design; improved; indexing; inflammatory marker; injured; insulin sensitivity; molecular marker; mortality; muscle stress; muscular structure; muscular system; myostatin; neuromuscular; novel; nutrition; portability; prevent; protein degradation; quadriceps muscle; rehabilitation strategy; response; sound; transcription factor

DESCRIPTION (provided by applicant): Novel Intervention to Influence Muscle Plasticity in Veterans with SCI The long-term goal is to develop a rehabilitation strategy to prevent the deleterious muscular and metabolic complications (diabetes) that follow individuals with complete spinal cord injury (SCI). Up to 300, 000 persons are living with SCI, and more than 10% receive their care within the VA health system. Secondary complications (muscle atrophy, and diabetes) in the decades after SCI cost society between 4 and 7 billion dollars annually. A method to prevent these complications would not only provide substantial savings, but also could profoundly improve the quality of life of veterans with SCI. Recently, we verified that a certain dose of muscle force maintained the calf muscle of the lower leg for over 2 years following SCI. We now aspire to determine if various doses of muscle force preferentially up regulate protein synthesis pathways, down regulate protein degradation pathways, and improve blood metabolic markers during a novel functional exercise. Three specific aims will address these hypotheses by inducing various doses of stress to the lower extremities during stance and neuromuscular electrical stimulation. Aim 1 will compare 3 tiers of muscle force training induced via (0, 10, and 20 Hz stimulation) on muscle physiological properties (fatigue, force, potentiation) over a 12 week training and detraining period. Aim 2 will compare the effects of 3 muscle forces (0, 10 Hz, 20 Hz) on molecular markers of muscle atrophy. Aim 3 will compare the effects of three muscle forces (0,. 10 Hz, and 20 Hz) on insulin sensitivity and inflammatory markers. The combined effect of cardiovascular stress through stance and muscle activation offers a unique strategy to affect metabolic changes. This study is novel because it uses an intervention that is feasible, quantifiable, portable, and dose of muscle force specific. This research is grounded by sound scientific principles, but also has the potential to rapidly translate to the VA health system to influence health quality. In the next several decades, a cure for spinal cord injury is a realistic possibility. Without a method to preserve the integrity of paralyzed lower limbs, the veterans with SCI injured today will be unable to participate in those trials because of a deteriorated musculoskeletal system. Moreover, preservation of muscular systems may increase insulin sensitivity and improve the veterans overall health today. We believe that future clinical trials will need the dose information from this trial to establish efficacy. This intervention has excellent potential for efficacy, but also is likely to be economical and easily integrated into the daily lives of veterans with SCI.

描述（由申请人提供）： 影响 SCI 退伍军人肌肉可塑性的新型干预措施 长期目标是制定康复策略，预防完全脊髓损伤 (SCI) 患者出现的有害肌肉和代谢并发症（糖尿病）。多达 300, 000 人患有 SCI，其中超过 10% 在 VA 卫生系统内接受护理。 SCI 后的几十年里，继发并发症（肌肉萎缩和糖尿病）每年给社会造成 4 至 70 亿美元的损失。预防这些并发症的方法不仅可以节省大量费用，还可以极大地改善患有 SCI 的退伍军人的生活质量。最近，我们证实一定剂量的肌肉力量在 SCI 后可以维持小腿小腿肌肉 2 年以上。我们现在渴望确定在一种新型功能锻炼过程中，不同剂量的肌肉力量是否会优先上调蛋白质合成途径、下调蛋白质降解途径并改善血液代谢标志物。三个具体目标将通过在站立和神经肌肉电刺激期间对下肢产生不同剂量的压力来解决这些假设。目标 1 将比较 12 周训练和放松期间通过（0、10 和 20 Hz 刺激）诱导的 3 层肌肉力量训练对肌肉生理特性（疲劳、力量、增强）的影响。目标 2 将比较 3 种肌肉力量（0、10 Hz、20 Hz）对肌肉萎缩分子标记的影响。目标 3 将比较三种肌肉力量（0、10 Hz 和 20 Hz）对胰岛素敏感性和炎症标志物的影响。心血管压力通过姿势和肌肉激活的综合作用提供了影响代谢变化的独特策略。这项研究是新颖的，因为它使用了一种可行、可量化、便携且针对肌肉力量剂量的干预措施。这项研究以合理的科学原理为基础，但也有可能迅速转化为退伍军人管理局的卫生系统，以影响健康质量。在接下来的几十年里，治愈脊髓损伤是一种现实的可能性。如果没有办法保持瘫痪下肢的完整性，今天遭受脊髓损伤的退伍军人将因肌肉骨骼系统恶化而无法参加这些试验。此外，保留肌肉系统可能会提高胰岛素敏感性并改善当今退伍军人的整体健康状况。我们相信，未来的临床试验将需要该试验的剂量信息来确定疗效。这种干预措施具有巨大的疗效潜力，而且可能经济且易于融入患有 SCI 的退伍军人的日常生活中。