Spinal cord injury (SCI) results in a number of deficits of motor and sensory systems, including paralysis, anaesthesisa, hyper-reflexia and spasticity below the level of the lesion. The proposed research will address critical issues related to the treatment and mechanisms of hyper-reflexia and spasticity. Preliminary evidence suggests that the onset of hyper-reflexia is not immediate, but rather the animal transitions to a hyper-reflexive state between 7-21 days after injury, as measured by frequency-dependent depression of the H-reflex in terminal experiments at specific time points. We can now verify the exact time point using longitudinal surface electrode recording of the H-reflex measuring frequency-dependent depression changes in the same transected animal. We have developed the capacity to assess spasticity using windup and velocity protocols for the stretch reflex, providing an additional functional measure of symptoms after SCI. Research at the Center for Translational Neuroscience (CTN) determined that passive exercise treatment using motorized bicycle exercise training (MBET) can be used to normalize reflex changes after SCI in the human and the animal model. MBET, initiated 7 days post injury, for thirty days post-injury for 1 hour sessions 5 days/week was found to prevent the loss of frequency-dependent depression usually seen after injury in the animal SCI model. We now want to determine the efficacy of MBET in the chronic animal model of SCI and the amount of time required to show rescue of reflex changes using the longitudinal surface recording technique. Novel preliminary evidence also suggests that L-DOPA given orallly can prevent hyper-reflexia measured by normalization in frequency-dependent depression of the H-reflex. PUBLIC HEALTH RELEVANCE Currently, over 200,000 Americans suffer from spinal cord injury (SCI), many of who suffer from excessive reflexes and spasticity which prevent effective recovery and rehabilitation efforts. The proposed research will use an animal model of SCI to determine when these excessive reflexes and spasticity appear and whether they can be modified by Motorized Bicycle Exercise Training (MBET) or L-dopa, a drug commonly used for individuals with Parkinson's disease. [unreadable] [unreadable] [unreadable] [unreadable]
NIH ExPorter
NIH ExPorter