Physical and Pharmacological Effects on Movement in SCI

SCI 运动的物理和药理作用

基本信息

批准号：
7039029
负责人：
Thomas George Hornby
金额：
$ 17.7万
依托单位：
REHABILITATION INSTITUTE OF CHICAGO D/B/A SHIRLEY RYAN ABILITYLAB
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-04-01 至 2009-03-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): There is extensive experimental history demonstrating that alteration in motor behaviors following spinal cord injury (SCI) may be partly a result of damage to descending neuromodulatory (in particular serotonergic and noradrenergic) inputs to spinal circuits. Agonists to these monoamines act on specific spinal pathways to modulate motor behaviors (including locomotion) and their responses to sensory information, and have been shown to play a critical role in enhancement of neural plasticity in locomotor circuits. While spontaneous healing and specific physical interventions (i.e., body-weight supported treadmill training, BWSTT) can facilitate return of motor control following motor incomplete SCI in humans, the combination of physical and pharmacological agents to alter motor recovery has yet to be studied in detail. Accordingly, we propose to study the role of selective serotonin reuptake inhibitors (i.e., SSRIs, fluoxetine) on volitional and spastic motor behaviors following chronic (> 1 yr. post) motor incomplete SCI in humans and their effects in combination with specific physical interventions (i.e., BWSTT). Aim 1 will provide quantitative assessment of isometric volitional motor output (maximal torque output, agonist/antagonist co-activation), involuntary spastic behaviors (parameters associated with hyperexcitable flexor and stretch reflexes), and kinematics and EMG activity during locomotion to be compared with clinical measurements of muscle strength, spasticity and quality of overground ambulation (level of assistance, devices used, speed and gait pattern) before and following administration of fluoxetine. Aim 2 will investigate the plasticity of these motor behaviors following 12 weeks of BWSTT using robotic assistance in combination with pharmacological manipulations. Changes in behaviors will be compared to a control group of subjects with motor incomplete SCI that do not receive pharmacological interventions. We expect the monoaminergic agents to depress excitability of selected afferent pathways, but enhance circuitry responsible for volitional motor output and locomotion, thereby expediting the recovery of locomotor capability with BWSTT. As a consequence of these findings, a radical change in pharmacological management of motor incomplete SCI will be indicated.

描述（由申请人提供）：大量的实验历史表明，脊髓损伤（SCI）后运动行为的改变可能部分是由于脊髓回路的下行神经调节（特别是血清素能和去甲肾上腺素能）输入受损所致。这些单胺的激动剂作用于特定的脊髓通路，调节运动行为（包括运动）及其对感觉信息的反应，并已被证明在增强运动回路的神经可塑性方面发挥着关键作用。虽然自发愈合和特定的物理干预（即体重支持的跑步机训练，BWSTT）可以促进人类运动不完全性 SCI 后运动控制的恢复，但物理和药物制剂相结合来改变运动恢复仍有待详细研究。因此，我们建议研究选择性血清素再摄取抑制剂（即 SSRIs、氟西汀）对人类慢性（> 1 年后）运动不完全性 SCI 后的意志和痉挛运动行为的作用，及其与特定物理干预措施相结合的效果。即 BWSTT）。目标 1 将提供等长意志运动输出（最大扭矩输出、激动剂/拮抗剂共同激活）、不自主痉挛行为（与过度兴奋的屈肌和牵张反射相关的参数）以及运动过程中的运动学和肌电图活动的定量评估，以与临床进行比较在给药之前和之后测量肌肉力量、痉挛和地上行走质量（辅助水平、使用的设备、速度和步态模式）氟西汀。目标 2 将使用机器人辅助结合药物操作来研究 12 周 BWSTT 后这些运动行为的可塑性。将行为变化与未接受药物干预的运动不完全性 SCI 受试者的对照组进行比较。我们预计单胺能药物会抑制选定传入通路的兴奋性，但会增强负责意志运动输出和运动的回路，从而加快 BWSTT 运动能力的恢复。这些发现的结果表明，运动不完全性 SCI 的药物治疗将发生根本性变化。