Interjoint coordination and compensation in rat locomotion using x-ray kinematics

描述（由申请人提供）：大鼠已经成为许多神经损伤模型的前沿，并且可能与脊髓损伤和周围神经损伤领域的下一个最大的生物医学突破有关。在生物医学研究界，研究啮齿动物特定疾病模型的突破性方法越来越普遍。然而，定量和机械地解决运动功能结果以测试更微妙和复杂的假设的能力目前尚不可用，也必须进一步发展。用皮肤标记测量整个肢体运动模式（运动学）来量化运动功能通常是运动科学其他领域的黄金标准。然而，当研究像老鼠这样的小型哺乳动物时，由于皮肤相对于底层骨骼的运动产生了很大的误差，这可能会带来一个问题。本项目的目标是开发和测试一种高速x射线运动学系统，用于量化特定周围神经损伤后大鼠后肢协调运动缺陷。实现这一目标将提供两个直接的、可交付的最终产品，这将影响与量化大鼠运动行为有关的生物医学研究领域：（目标1）开发x射线运动分析，这将为大鼠运动模式提供黄金标准，并为更常见的皮肤标记运动学方法提供背景；（目标2）为理解特定神经肌肉损伤（如肌肉去神经支配）后运动补偿的基本原理提供理论基础。本课题的长期目标是为准确研究神经损伤后短期代偿、长期代偿和感觉反馈对运动控制的不同贡献提供一种手段。本项目的研究结果可以很容易地应用于小鼠的运动研究，对数百种基因敲除小鼠模型的运动研究具有重要意义，有助于推进大鼠运动功能的研究。这项工作将产生能够精确量化运动缺陷的技术，这些运动缺陷可以映射到细微的神经肌肉病变，并为研究更复杂病变（如坐骨神经损伤或脊髓损伤）的恢复机制奠定理论基础，最终适用于转基因大鼠和小鼠。大鼠和小鼠是研究和开发脊髓损伤和其他严重的、使神经系统衰弱的损伤的治疗方法的首选研究模型。目前还不存在将特定的神经肌肉损伤与特定的大鼠生物力学步态缺陷联系起来的能力，因此科学界只能对潜在治疗的疗效做出一般结论。该项目：(1)将产生能够准确量化与非常具体的神经肌肉损伤相关的生物力学步态缺陷的技术；(2)为理解更复杂损伤（如脊髓损伤）中的神经力学补偿机制以及应用于步态障碍遗传原因的潜力提供理论基础。

DESCRIPTION (provided by applicant): The rat has come to the forefront of many nerve injury models and will likely be associated with the next greatest biomedical breakthroughs in the areas of spinal cord injury and peripheral nerve injury. Groundbreaking methods for studying specific disease models in rodents are increasingly prevalent in the biomedical research community. However, the ability to quantitatively and mechanistically resolve locomotor functional outcomes to test more subtle and sophisticated hypotheses is currently unavailable and must also be further developed. Measuring whole limb movement patterns (kinematics) with skin markers to quantify locomotor function is often the gold standard in other areas of movement science. However, this can present a problem when studying small mammals like rats due to the large errors attributed to movement of the skin relative to the underlying skeleton. The objectives of this project are to develop and test a high-speed x-ray kinematics system for quantifying locomotor deficits in rat hindlimb coordination after specific peripheral nerve injuries. Achieving this objective will provide two immediate, deliverable end-products that will impact areas of biomedical research concerned with quantifying locomotor behavior in rats: (Aim 1) development of an x-ray kinematics locomotor assay that will provide a gold standard for rat locomotor patterns and provide context for the more common skin marker kinematics methods; and, (Aim 2) a theoretical foundation for understanding basic principles of locomotor compensation after specific neuromuscular injuries such as a muscle denervation. The long-term goals of this project are to provide a means to accurately study the different contributions of short-term compensation, long-term compensation and sensory feedback to the control of locomotion after nerve injury. In advancing the study of locomotor function in rats, the results of this project could easily be applied to mouse locomotion and have great implications for the study of locomotion in the hundreds of genetic knockout mouse models. This work will generate technology capable of accurately quantifying motor deficits that map to subtle neuromuscular lesions and form a theoretical basis for studying the mechanisms that drive recovery in more complex lesions such as sciatic nerve injury or spinal cord injury, with eventual applicability to genetically modified rats and mice. Rats and mice are overwhelmingly the research model of choice to study and develop therapies for spinal cord injury and other serious, debilitating insults to the nervous system. Currently the ability to relate specific neuromuscular injuries to specific biomechanical gait deficits in rats does not exist, so the scientific community can only make general conclusions about the efficacy of potential treatments. This project: (1) will generate technology capable of accurately quantifying biomechanical gait deficits that relate to very specific neuromuscular injuries, and (2) generate a theoretical basis for understanding the neuromechanical compensation mechanisms in more complicated injuries such as spinal cord injury and potential for application to genetic causes of gait disorders.