Novel Intervention to Influence Muscle Plasticity in Veterans with SCI

描述（由申请人提供）： 影响脊髓损伤退伍军人肌肉可塑性的新干预措施长期目标是制定一种康复策略，以预防完全性脊髓损伤（SCI）患者出现有害的肌肉和代谢并发症（糖尿病）。多达300，000人患有脊髓损伤，超过10%的人在退伍军人管理局卫生系统接受治疗。SCI后几十年的继发性并发症（肌肉萎缩和糖尿病）每年花费社会40亿至70亿美元。预防这些并发症的方法不仅可以节省大量资金，还可以大大改善SCI退伍军人的生活质量。最近，我们证实了一定剂量的肌肉力量维持小腿肌肉超过2年后SCI。我们现在渴望确定在一种新的功能性运动中，不同剂量的肌肉力量是否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。三个具体的目标将解决这些假设，诱导不同剂量的压力，下肢在立场和神经肌肉电刺激。目的1将比较在12周训练和停止训练期间通过（0、10和20 Hz刺激）诱导的3级肌肉力量训练对肌肉生理特性（疲劳、力量、增强）的影响。目的2比较3种肌力（0、10 Hz、20 Hz）对肌肉萎缩分子标志物的影响。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。通过站立和肌肉激活的心血管压力的组合效应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的、可量化的、便携式的、针对肌肉力量的干预措施。这项研究是基于健全的科学原则，但也有可能迅速转化为VA卫生系统，以影响健康质量。在接下来的几十年里，治愈脊髓损伤是一个现实的可能性。如果没有一种方法来保持瘫痪下肢的完整性，今天受伤的脊髓损伤退伍军人将无法参加这些试验，因为恶化的肌肉骨骼系统。此外，保留肌肉系统可以增加胰岛素敏感性，改善退伍军人的整体健康状况。我们认为，未来的临床试验将需要本试验的剂量信息来确定疗效。这种干预具有很好的疗效潜力，但也可能是经济的，很容易融入SCI退伍军人的日常生活。

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.