Re-training locomotor circuitry in a rat model of Spinal Cord Injury

在脊髓损伤大鼠模型中重新训练运动回路

• 批准号: 7575679
• 负责人: David SK Magnuson
• 金额: $ 29.1万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-15 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7575679
• 关键词: Animal Model; Animals; Articular Range of Motion; Axon; Body Weight; Canes; Complex; Contusions; Custom; Cutaneous; Dorsal; Feedback; Felis catus; Flexor; Frequencies; Generations; Golgi Tendon Organs; Hindlimb; Hip region structure; Human; Individual; Injury; Joint Capsule; Lead; Learning; Left; Leg; Length; Limb structure; Link; Locomotion; Locomotor Recovery; Lumbar spinal cord structure; Messenger RNA; Methods; Modeling; Motor; Motor Activity; Motor Neurons; Motor output; Movement; Muscle; Muscle Spindles; Nerve; Nervous system structure; Output; Pathway interactions; Patients; Pattern; Phase; Physiological; Play; Positioning Attribute; Principal Investigator; Process; Protocols documentation; Rattus; Recovery of Function; Rehabilitation therapy; Relative (related person); Research Personnel; Role; Speed; Spinal Cord; Spinal cord injury; Staging; Stress; Surface; Swimming; Testing; Therapeutic; Tissues; Training; Walkers; Walking; Water; Weight; Weight-Bearing state; Work; base; foot; functional improvement; human subject; improved; injured; neuronal circuitry; programs; receptor; rehabilitation strategy; research study; response; success

DESCRIPTION (provided by applicant): One of the most promising therapeutic strategies for spinal cord injury is weight-supported treadmill training. This rehabilitation therapy seeks to re-train the spinal cord circuitry below the level of injury to participate in functional locomotion. The mammalian spinal cord, humans included, contains complex neuronal circuitry that participates in the generation of the repeating pattern of motor activity (step-cycle) associated with normal over-ground locomotion. Both animal and human studies have demonstrated that moving the hindlimbs to mimic normal walking, usually on a treadmill with rehabilitation assistants, can lead to improved hindlimb locomotor function. However, the treadmill speed that is used is very slow compared to normal walking and much of the body weight of the animal or patient must be supported externally. Consequently, relatively few step-cycles are generated during a re-training session, certainly far fewer than normal walking. We hypothesized that a re-training strategy that allowed for many more step-cycles to be completed would be more effective and that re-training the locomotor circuitry would be much more successful. Some of the components that are thought to be important for the re-training process include step-cycle number, cutaneous feedback from the foot, limb position, and weight-bearing feedback from the leg. How each of these individual components contribute to successful rehabilitation, and the physiological and cellular mechanisms underlying the re-training process are not known. We have devised a strategy to use buoyancy during swimming to provide weight-support which allows for high numbers of step-cycles to be completed during a rehabilitation session. We have also incorporated a simple approach to provide phasic cutaneous feedback during swimming and partial limb-loading (weight- bearing) during walking in shallow water. We hope to uncover what relative contributions step-cycle number and frequency, cutaneous feedback and limb-loading make to the overall success of a locomotor rehabilitation strategy. In addition, we will begin to look at the mechanisms of rehabilitation associated plasticity using a custom made array to detect changes in mRNA levels in spinal cord tissue following different training protocols.

描述（由申请人提供）：脊髓损伤最有前途的治疗策略之一是体重支持的跑步机训练。这种康复疗法旨在重新训练脊髓回路以下，以低于损伤水平，以参与功能运动。哺乳动物的脊髓（包括人）包含复杂的神经元电路，参与与正常地面运动相关的运动活动（步骤）重复模式的产生。动物和人类研究都表明，将后肢移至模仿正常步行，通常在带有康复助手的跑步机上，可以改善后肢运动功能。但是，与正常步行相比，使用的跑步机速度非常慢，并且必须在外部支撑动物或患者的大部分体重。因此，在重新训练期间产生相对较少的阶梯循环，肯定比正常步行少得多。我们假设，重新训练的策略允许完成更多的阶梯循环，将更有效，重新训练运动电路将更加成功。人们认为对于重新训练过程很重要的某些组件包括阶梯循环数，脚下的皮肤反馈，肢体位置以及腿部的承重反馈。这些单个组件中的每一个如何有助于成功的康复，以及重新训练过程的生理和细胞机制尚不清楚。我们已经制定了一种在游泳期间使用浮力的策略，以提供体重支持，该策略允许在康复期间完成大量的阶梯循环。我们还结合了一种简单的方法，可以在游泳和部分肢体加载（重量轴承）中提供阶段性皮肤反馈，在浅水中行走时。我们希望揭示对运动康复策略的整体成功的阶梯循环数量和频率，皮肤反馈和肢体加载的影响。此外，我们将使用定制的阵列开始研究康复与可塑性的机制，以检测不同训练方案后脊髓组织中mRNA水平的变化。