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. ? ? ?
