AR CAREER DEVELOPMENT COBRE: PALLIATIVE STRATEGIES IN SPINAL CORD INJURY

AR 职业发展 COBRE：脊髓损伤的姑息策略

• 批准号: 7960488
• 负责人: Thomas S Kiser
• 金额: $ 22.8万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960488
• 关键词: Acute; Animals; Ankle; Baclofen; Behavior; Bicycling; Centers of Research Excellence; Chronic; Computer Retrieval of Information on Scientific Projects Database; DEXA; Data; Decubitus ulcer; Doctor of Philosophy; Exercise; Frequencies; Funding; Goals; Grant; H-Reflex; Home environment; Hospitals; Human; Hyperreflexia; Individual; Infective cystitis; Injury; Institutes; Institution; Intervention; Intestines; Leg; Magnetic Resonance Imaging; Measures; Mediating; Medical History; Monitor; Muscular Atrophy; Neurologic; Osteoporosis; Pain; Patients; Protocols documentation; Quality of life; Rattus; Recovery; Recruitment Activity; Recurrence; Reflex action; Rehabilitation therapy; Research; Research Personnel; Residual state; Resources; Savings; Scanning; Services; Source; Spinal; Spinal Cord transection injury; Spinal cord injury; Spinal cord injury patients; Testing; Training; United States National Institutes of Health; career development; depression; design; improved; muscle form; novel; palliative; programs; research study; translational neuroscience; treatment strategy

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. HUMAN STUDIES- T. Kiser, MD This project is a human research study on subjects with spinal cord injury (SCI) aimed at establishing the optimal treatment strategies testing the effects of a passive motorized bicycle exercise program conducted in the individuals' homes. This Project will assess the effects of this therapy in improving neurologic recovery and decreasing secondary complications. We have designed a motorized bicycle exercise trainer (MBET) that can be used in the home and are developing a way to measure for compliance and other measures of use. The main hypothesis to be tested is that long-term MBET will increase muscle mass, reduce hyperreflexia and spasticity, as well as reduce the complications common to SCI. Specific Aim 1: We will measure and compare changes in leg muscle mass measured by MRI in groups of 2 "Chronic" (greater than one year after injury) patients who will undergo MBET for 25 weeks. These studies will determine if long-term MBET has salutary effects on muscle mass. After the end of testing, we will stop MBET and measure muscle mass to determine salutary effects, then again 12 weeks later to determine regression or savings in muscle mass. Every 6 months, another group of 2 patients will begin MBET for a total of 8 Chronic patients. An equal number of Chronic control SCI patients will be tested. Specific Aim 2: The use of MBET was found also to increase habituation of the H-reflex (the electrophysiological equivalent of the ankle reflex), and may thus offer relief from hyperreflexia. We will test the effects of MBET for changes in H-reflex habituation, spasticity measures, and a potential decrease in the amount of baclofen needed to reduce spasticity in the same groups of "Chronic" SCI patients. These studies will determine if MBET has differential effects on the modulation of spinal circuitry mediating reflex behavior. Each group of subjects in Aim 1 will be tested every 2 to 4 weeks for H-reflex and spasticity/baclofen changes during the 25-week test period, and also during the 12-week post-MBET period. These data will reveal levels of regression or savings in reflex and spasticity measures resulting from MBET therapy. Specific Aim 3: The secondary complications of pressure sores, pain, osteoporosis, bowel impactions and recurrent bladder infections are common in SCI. We will assess the medical history of these complications, conduct a physical exam to assess for pressure sores before and after MBET, and conduct a DEXA scan to assess for osteoporosis before and after the MBET program to determine its effect on osteoporosis. Specific Aim 4: Recruit one "Acute" subject every 6 months from the SCI service at our rehabilitation hospital to participate in an acute SCI MBET protocol. The aim is to institute MBET within 4-6 weeks after injury (before hyperreflexia and significant muscle atrophy sets in), and monitor H-reflex, spasticity scores and secondary complications for 25 weeks, then stop MBET but monitor all measures for 12 weeks to determine regression or savings. An equal number of Acute control subjects will be tested. These subjects will be tested at two-week intervals until reflexes stabilize. ANIMAL STUDIES- N.B. Reese, PT, PhD The long-term goal of Project IV is to develop a Spinal Cord Injury (SCI) Mobilization Program for increasing the quality of life of SCI victims. We have designed parallel human and animal studies aimed at establishing the optimal treatment strategies for regaining certain functions, testing the effects of different therapies in humans while exploring novel potential palliative strategies on animals. The animal studies have focused on the effects of passive exercise, in the form of motorized bicycle exercise training (MBET), on low-frequency depression of the H-reflex (hyperreflexia) in rats following spinal cord transection. The effects of MBET on low-frequency depression of the H-reflex have been tested following initiation of exercise in acutely transected and chronically transected animals. In addition, we have examined the residual effects of exercise on the H-reflex once the exercise intervention is terminated. This Project is allowing us to assess the effects of both "early" rehabilitation efforts and "late" rehabilitation efforts in improving neurologic recovery and decreasing secondary complications such as hyperreflexia.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 人类研究 - T. Kiser，医学博士 该项目是一项针对脊髓损伤 (SCI) 受试者的人体研究，旨在建立最佳治疗策略，测试在个人家中进行的被动机动自行车锻炼计划的效果。该项目将评估该疗法在改善神经功能恢复和减少继发并发症方面的效果。 我们设计了一款可在家中使用的电动自行车运动训练器 (MBET)，并正在开发一种测量依从性和其他使用措施的方法。 待检验的主要假设是，长期 MBET 会增加肌肉质量，减少反射亢进和痉挛，并减少 SCI 常见的并发症。 具体目标 1：我们将测量并比较 2 名“慢性”（受伤后一年以上）患者的 MRI 测量的腿部肌肉质量的变化，这些患者将接受 25 周的 MBET。 这些研究将确定长期 MBET 是否对肌肉质量产生有益影响。 测试结束后，我们将停止 MBET 并测量肌肉质量以确定有益效果，然后在 12 周后再次测量以确定肌肉质量的回归或节省。 每 6 个月，另一组 2 名患者将为总共 8 名慢性病患者开始 MBET。 将测试同等数量的慢性对照 SCI 患者。 具体目标 2：发现使用 MBET 还可以增加 H 反射（相当于踝反射的电生理学）的习惯，从而可以缓解反射亢进。 我们将测试 MBET 对 H 反射习惯变化、痉挛测量的影响，以及在同一组“慢性”SCI 患者中减少痉挛所需的巴氯芬用量的潜在减少。 这些研究将确定 MBET 对介导反射行为的脊髓回路的调节是否有不同的影响。 目标 1 中的每组受试者将在 25 周测试期间以及 MBET 后 12 周期间每 2 至 4 周测试一次 H 反射和痉挛/巴氯芬变化。 这些数据将揭示 MBET 疗法导致的反射和痉挛测量的回归或节省水平。 具体目标 3：压疮、疼痛、骨质疏松、肠嵌塞和复发性膀胱感染等继发并发症在 SCI 中很常见。 我们将评估这些并发症的病史，在 MBET 之前和之后进行体检以评估压疮情况，并在 MBET 计划之前和之后进行 DEXA 扫描以评估骨质疏松症，以确定其对骨质疏松症的影响。 具体目标 4：每 6 个月从我们康复医院的 SCI 服务中招募一名“急性”受试者来参加急性 SCI MBET 方案。 目标是在受伤后 4-6 周内（在反射亢进和显着肌肉萎缩出现之前）开始 MBET，并监测 H 反射、痉挛评分和继发并发症 25 周，然后停止 MBET，但监测所有措施 12 周，以确定回归或节省。 将测试同等数量的急性对照受试者。 这些受试者将每隔两周接受一次测试，直到反应稳定。 动物研究 - 注意里斯，PT，博士 项目 IV 的长期目标是制定脊髓损伤 (SCI) 动员计划，以提高 SCI 受害者的生活质量。 我们设计了平行的人类和动物研究，旨在建立恢复某些功能的最佳治疗策略，测试不同疗法对人类的效果，同时探索对动物的新的潜在姑息策略。 动物研究的重点是机动自行车运动训练 (MBET) 形式的被动运动对脊髓横断后大鼠 H 反射（反射亢进）低频抑制的影响。 已经在急性横断和慢性横断动物开始运动后测试了 MBET 对 H 反射低频抑制的影响。 此外，我们还检查了运动干预终止后运动对 H 反射的残留影响。 该项目使我们能够评估“早期”康复工作和“晚期”康复工作在改善神经功能恢复和减少反射亢进等继发并发症方面的效果。