Neuro-Musculoskeletal Plasticity after SCI

描述（由申请人提供）：长期目标是制定一种康复策略，以防止完全性脊髓损伤（SCI）后有害的神经、肌肉和骨骼继发性并发症。每年有多达2万名美国人患有脊髓损伤，使其成为最重要的公共卫生问题。在脊髓损伤后的几十年里，继发性并发症（肌肉萎缩、骨质疏松、骨折、痉挛）每年给社会造成40到70亿美元的损失。一种预防这些并发症的方法不仅可以节省大量资金，还可以极大地提高脊髓损伤患者的生活质量，并使他们成为未来治疗的可行候选人。最近，我们证实了一定剂量的应力可以在脊髓损伤后的2年内保护小腿的骨和肌肉生理。这些发现表明，在瘫痪后早期对整个下肢施加不同剂量的肌肉应力的新方法可能是脊髓损伤停用后形成脊髓回路、肌肉和骨重组的重要机制。三个特定的目标将测试这些假设，使用一种创新的方法，在站立时使用神经肌肉电刺激诱导不同剂量的压力到下肢。目的1将比较三种肌肉应激剂量（0、40、80%体重）对脊髓损伤后第一年肌肉生理特性（疲劳、力、增强）的影响。目标2将比较4种应激剂量（0、40、80和120%体重）对脊髓损伤后第一年骨密度的影响。目的3将比较不同剂量的肌肉应激对脊髓损伤后第一年痉挛性高张力和h反射抑制的影响。本研究的新颖之处在于其对可行性和剂量特异性的强调。这项研究以科学原理为基础，但也有可能迅速转化为临床环境，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。如果没有一种方法来保持瘫痪的下肢的完整性，那么即使找到了治疗方法，今天的脊髓损伤患者也将成为“不合适的候选者”，无法重新站立和行走。在此期间，脊髓损伤后神经、肌肉和骨骼特性的保存可能有助于个体的健康。该方法不仅具有极好的疗效潜力，而且经济实惠，易于融入脊髓损伤患者的日常生活。

DESCRIPTION (provided by applicant): The long-term goal is to develop a rehabilitation strategy to prevent the deleterious neural, muscular, and skeletal secondary complications that follow complete spinal cord injury (SCI). As many as twenty thousand Americans sustain an SCI each year, making it a public health concern of primary importance. Secondary complications (muscle atrophy, osteoporosis, bone fractures, spasticity) 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 could also profoundly improve the quality of life of people with SCI and keep them as viable candidates for the future cure. Recently, we verified that a certain dose of stress preserved bone and muscle physiology in the lower leg for 2 years following SCI. These findings suggest that a novel approach to apply various doses of muscle stress to the entire lower extremities early after paralysis may be an important mechanism to shape spinal circuitry, muscle, and bone reorganization following disuse from SCI. Three specific aims will test these hypotheses using an innovative method to induce various doses of stress to the lower extremities during stance using neuromuscular electrical stimulation. Aim 1 will compare 3 doses of muscle stress (0, 40, 80% BW) on muscle physiological properties (fatigue, force, potentiation) over the first year following SCI. Aim 2 will compare 4 doses of stress (0, 40, 80, and 120% BW) on skeletal bone mineral density over the first year following SCI. Aim 3 will compare various doses of muscle stress on spastic hypertonia and H-reflex suppression over the first year following SCI. A novel component of this study is its emphasis on feasibility and dose specificity. This research is grounded in scientific principles, but also has the potential to rapidly translate to the clinical milieu 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, people injured today with SCI will be left as "inappropriate candidates" for reintroduction to standing and walking, should a cure be found. In the interim, preservation of neural, muscular, and skeletal properties after SCI may contribute to a healthier individual. The proposed method not only has excellent potential for efficacy, but is also likely to be economical and easily integrated into the daily lives of people with SCI.