PALLIATIVE STRATEGIES IN SPINAL CORD INJURY

脊髓损伤的姑息策略

• 批准号: 6972186
• 负责人: Thomas S Kiser
• 金额: $ 34.58万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-16 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6972186
• 关键词: behavioral /social science research tag; behavioral habituation /sensitization; biomechanics; body composition; body movement; chordate locomotion; clinical research; combination therapy; electromyography; electrostimulus; exercise; functional ability; human subject; human therapy evaluation; laboratory rat; levodopa; muscle strength; nonhuman therapy evaluation; rehabilitation; shear stress; spinal cord injury; spinal reflex; therapy design /development

Recent human clinical application of our epidural spinal cord stimulation (ESCS) technology was found to promote locomotion without fatigue for as long as 300 m with the aid of only a walker in a SCI patient. Our previous studies had shown that ESCS in acutely transected animals induced treadmill stepping. More recently, we found that passive exercise training in adult spinal cord transected rats led to maintenance of muscle mass (i.e. prevented muscle atrophy) and restored habituation of the H-reflex (i.e. decreased hyperreflexia). The proposed research is designed to develop a SCI Mobilization Program for humans, at first testing partial weight bearing training (PWBT) and motorized bicycle exercise training (MBET) for their effects, singly and in combination, on locomotor activity and H-reflex habituation in SCI patients. We will measure and compare increases in muscle mass, improvements in step cycle parameters, changes in motor and sensory indices, and changes in H-reflex habituation and spasticity. Future studies will include ESCS and other potential therapies. We will also test in animals additional potential palliative strategies for SCI. Recently, we tested successfully the possibility of combining 1) MBET, 2) ESCS and 3) oral L-dopa therapy to promote locomotion in transected adult rats. Preliminary data indicate that this combination of therapies may prove efficacious in the restoration of stepping following complete spinal transection in the rat. The variable to be measured is electromyographic (EMG) activity in the hindlimbs, with analysis of muscle burst timing and amplitude, and step cycle frequency and duration, induced following each form of treatment or combined therapy. Data will be generated using an established model of SCI in the rat. These studies will provide essential information regarding the optimal combination of pharmacological intervention, exercise duration, and electrical stimulation parameters of the spinal cord necessary to maximize recovery of spinal locomotion following SCI. There is great potential for such information to translate into improved rehabilitation strategies for the human patient with SCI. An indirect benefit of these therapies may be the reduction of hyperreflexia, and presumably spasticity, in some patients with SCI (with concomitant reduction in baclofen therapy). The proposed research will generate pilot data in multiple important areas for securing future R01 support.

在SCI患者中，发现我们的硬膜外脊髓刺激（ESC）技术的最新人类临床应用可在不疲劳的情况下促进不疲劳的运动。我们以前的研究表明，急性转移动物的ESC诱发跑步机阶梯。最近，我们发现，成年脊髓转移大鼠进行的被动运动训练导致肌肉质量维持（即预防肌肉萎缩），并恢复了H反射的习惯（即降低了超反射症）。拟议的研究旨在为人类开发一项针对人类的SCI动员计划，在首次测试部分负重训练（PWBT）和机动的自行车运动训练（MBET），以单独和结合，对SCI患者的运动和H-Reflex习惯。我们将测量和比较肌肉质量的增加，步骤周期参数的改善，运动指数的变化以及H反射习惯和痉挛的变化。未来的研究将包括ESC和其他潜在疗法。我们还将在动物中测试SCI的其他潜在姑息策略。最近，我们成功地测试了结合1）MBET，2）ESC和3）口服L-DOPA疗法的可能性，以促进跨性成年大鼠的运动。初步数据表明，这种疗法的组合可能在大鼠完全脊柱横断后恢复阶梯的恢复有效。要测量的变量是后肢中的肌电图（EMG）活性，分析了肌肉爆发的时机和振幅，以及遵循每种形式的治疗或联合治疗诱导的步骤循环频率和持续时间。数据将使用大鼠中的SCI模型生成。这些研究将提供有关药理学干预，运动持续时间和电刺激参数最佳组合的基本信息，以最大程度地提高SCI后脊柱运动的恢复。此类信息有很大的潜力可以转化为SCI患者的改进的康复策略。这些疗法的间接益处可能是一些SCI患者的过度反射症和痉挛的降低（巴氯芬疗法的降低）。拟议的研究将在多个重要领域生成试验数据 确保未来的R01支持。