B. Abstract Traumatic injuries to peripheral nerves affect hundreds of thousands of Americans each year. Even though axons in injured nerves can regenerate, complete functional recovery following traumatic nerve injuries is rare. Novel treatments are needed. One such treatment is exercise. If applied immediately following nerve injury, exercise in the form of treadmill training results in enhancement of axon regeneration. However, its effects on the long-lasting changes in circuitry in the central nervous system (CNS) that accompanies nerve injury and on functional recovery are less clear. The overall goal ofthis project is to determine the efficacy of exercise as a therapy for traumatic peripheral nerve injuries. The significance of changing the timing, dose, and pattern of exercise applied on the injury-induced change in spinal circuitry and on functional recovery after nerve injury will be studied. The sciatic nerve in rats will be cut and repaired by end-to-end anastomosis. The time course and extent of recovery of muscle reinnervation and spinal reflexes will be monitored using electrophysiological recordings from awake animals. Functional recovery will be assessed by measurement of hindlimb movements and timing and intensity of activity of reinnervated muscles during locomotion, and will focus on the ability of animals to adapt to walking up or down slopes. The influence of exercise on CNS changes will be studied using immunohistofluorescence. The significance of altering the timing and duration of post-denervation exercise will be studied in Aim 1.
In Aim 2, different doses of exercise will be applied by using upslope and downslope treadmill training. The influence of the pattern of exercise applied in male and female rats will be studied in Aim 3. The outcomes of these experiments are expected to result in the formulation of effective strategies for exercise as a treatment for peripheral nerve injury that can be translated to different types of injuries and to clinical application.
The results of this Project will be critical new knowledge of the efficacy of treadmill walking as a novel therapy for treatment of peripheral nerve injuries. By establishing the therapeutic window, dosing, and pattern of exercise required to promote both enhanced regeneration and shaping of spinal circuitry, these results will contribute to increasing the translational potential of this innovative treatment strategy.
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