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

描述（由申请人提供）：脊髓损伤最有希望的治疗策略之一是负重跑步机训练。这种康复疗法旨在重新训练受伤水平以下的脊髓回路，以参与功能性运动。包括人类在内的哺乳动物脊髓包含复杂的神经元回路，其参与与正常地面运动相关的运动活动的重复模式（步循环）的产生。动物和人类研究都表明，移动后肢以模仿正常行走，通常在康复助手的跑步机上，可以改善后肢运动功能。然而，与正常行走相比，所使用的跑步机速度非常慢，并且动物或患者的大部分体重必须由外部支撑。因此，在再训练期间产生相对较少的步周期，肯定比正常行走少得多。我们假设，允许完成更多步周期的再训练策略将更有效，并且重新训练运动回路将更成功。一些被认为对再训练过程很重要的组成部分包括步循环数、来自足部的皮肤反馈、肢体位置和来自腿部的负重反馈。这些单独的组成部分如何有助于成功的康复，以及再训练过程的生理和细胞机制尚不清楚。我们设计了一种策略，在游泳过程中使用浮力来提供重量支撑，从而允许在康复过程中完成大量的步周期。我们还采用了一种简单的方法，在游泳过程中提供阶段性皮肤反馈，在浅水中行走时提供部分肢体负荷（负重）。我们希望揭示步周期数和频率，皮肤反馈和肢体负荷的相对贡献，使运动康复策略的整体成功。此外，我们将开始研究康复相关的可塑性机制，使用定制的阵列来检测不同训练方案后脊髓组织中mRNA水平的变化。

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.