A Rodent Model for Locomotor Training with FNS

这项工作的长期目标是制定使用瘫痪肌肉的功能性神经肌肉刺激（FNS）的策略，以促进不完全性脊髓损伤个体的恢复。提出这项工作的动机是三个重要的发展。首先，最近的基础科学和临床研究表明，损伤脊髓的功能恢复程度取决于脊髓神经输入的活动模式。其次，最近的进展已经产生了FNS系统的自适应控制器，它提供了一种自动调节刺激参数的方法，以可靠地实现指定的节奏运动。第三，啮齿类动物脊髓损伤模型（完整和不完整损伤）在分子、细胞和系统水平上被广泛用于研究创伤性损伤的影响并评估治疗干预的结果。结合FNS运动训练和药物干预的联合治疗可能是增强脊髓外伤后脊髓回路重组（可塑性）最有效的方法。FNS辅助运动的啮齿动物模型将有助于定量评估包括FNS在内的治疗方案，并将提供表征FNS辅助运动对损伤脊髓神经解剖学和神经生理学影响的能力。这项生物医学工程研究拨款提案将开发一种啮齿类动物运动训练模型，该模型利用跑步机行走和功能性神经肌肉刺激（FNS）与固定模式和自适应控制器。完整动物的运动学和肌电图（EMG）模式将被检查，然后用于开发fns辅助运动的刺激模式。我们将利用FNS刺激脊椎化大鼠后肢肌肉来完成一系列的任务。在有部分重量支持的脊髓化大鼠中，这些任务的难度将从控制悬浮的后肢运动到控制跑步机运动中的后肢运动。每次运动将使用两种不同的FNS控制策略：固定模式或开环刺激模式和自适应刺激控制系统。自适应刺激控制系统将建立在我们之前的工作基础上，并有望提供更准确和更可重复的运动模式。该项目的成功完成将为fns辅助运动训练提供一种新的动物模型，并为评估运动行为提供定量方法。在未来的研究中，我们计划使用fns辅助运动的不完全性脊髓损伤啮齿动物模型来验证fns辅助运动训练促进不完全性脊髓损伤后运动恢复的假设。我们预计，自适应控制系统提供的改进性能可能会增强该技术的治疗效果。这种运动训练也可以与药物干预、组织移植和神经修复治疗相结合，以确定运动训练是否可以提高这些治疗的有效性。

The long-term goal of this work is to develop strategies for using functional neuromuscular stimulation (FNS) of paralyzed muscles to enhance the recovery of individuals with incomplete spinal cord injury. The proposed work is motivated by three important developments. First, recent basic science and clinical studies have demonstrated that the degree of functional recovery of the injured spinal cord depends on the activity patterns of neural inputs to the spinal cord. Second, recent advances have produced adaptive controllers for FNS systems that provide a means of automatically adjusting stimulation parameters to reliably achieve specified rhythmic movements. Third, rodent models of spinal cord injury (complete and incomplete lesions) are extensively being used at the molecular, cellular, and systems level to investigate the effects of traumatic injury and to assess the results of therapeutic intervention. A combination therapy that utilizes locomotor training with FNS and pharmacological intervention is likely to be the most effective in enhancing the reorganization (plasticity) of the spinal circuitry that is spared after spinal trauma. A rodent model for FNS-assisted locomotion would facilitate quantitative evaluation of therapeutic regimens that include FNS and would provide the ability to characterize effects of FNS-assisted locomotion on the neuroanatomy and neurophysiology of the injured spinal cord. This biomedical engineering research grant proposal will develop a rodent model of locomotor training that utilizes treadmill walking and functional neuromuscular stimulation (FNS) with fixed-pattern and adaptive controllers. Kinematic and electromyogram (EMG) patterns of intact animals will be examined and then used to develop stimulation patterns for FNS-assisted movement. A series of tasks will be performed using FNS stimulation of hindlimb muscles in spinalized rats. These tasks will progress in difficulty from controlling suspended hindlimb movements to controlling hindlimb movements during treadmill locomotion in spinalized rats with partial weight support. Two different FNS control strategies will be used for each movement: a fixed-pattern, or open-loop, stimulation pattern and an adaptive stimulation control system. The adaptive stimulation control system will build upon our previous work and is expected to provide movement patterns that are more accurate and more repeatable. Successful completion of the proposed project will result in a novel animal model for FNS-assisted locomotor training and provide quantitative methods for evaluating locomotor behavior. In future studies, we plan to use a rodent model of incomplete spinal cord injury with FNS-assisted locomotion to test the hypothesis that FNS-assisted locomotor training enhances motor recovery after incomplete spinal cord injury. We anticipate that the improved performance provided by the adaptive control system may enhance the therapeutic effects of the technique. This locomotor training could also be combined with pharmacological intervention, tissue transplant, and neural repair therapies to determine if locomotor training can enhance the effectiveness of these therapies.