Behavioral and molecular responses to high-intensity exercise in humans with iSCI

Northwestern University At Chicago, Evanston IL

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Abstract

DESCRIPTION (provided by applicant): Spinal cord injury (SCI) results in profound impairments in strength and sensation which can lead to the loss of independent mobility and decreased participation in daily activities. Following incomplete SCI, a primary goal of many patients is to regain independent walking ability. Both task specificity and amount of practice are known to have critical roles in the efficacy of locomotor recovery-based interventions after neurological injury. A significant intervention parameter that has yet to be thoroughly explored in humans with neurological injury is the intensity, or power output, of locomotor-based interventions. Studies in animal models of SCI have demonstrated that high-intensity locomotor practice results in an increased expression of neurotrophic factors, improved neuronal connectivity, and the recovery of stepping. Furthermore, the production of neurotrophic factors has also been suggested to be influenced by the neuromodulator serotonin. These findings suggest that locomotor intensity and serotonin signaling in spinal circuitry may be manipulated to potentiate neural plasticity and improve recovery of functional movement following SCI, although rigorous examination of intensity-related effects has not yet been conducted in humans. A previous limitation to the performance of high-intensity exercise regimens in neurological populations is the notion that such activities will lead to increased spastic motor behaviors and result in abnormal movement patterns. However, the acute and chronic effects of intensity on locomotor performance have yet to be well characterized. Therefore, the proposed aims will fill this gap in knowledge and evaluate the effects of locomotor exercise intensity on behavioral and molecular parameters, in addition to the effect of serotonin on the latter. This wil be achieved through the measurement of joint kinematics, coordination, muscle activity, metabolic activity, and serum levels of neurotrophic factors during a graded-intensity locomotor paradigm. The measurements will be collected under baseline conditions, following chronic high-intensity training, and again while exercise is paired with acute pharmacological manipulation of serotonin levels. This information will improve our understanding of the effect of intervention intensity in humans with incomplete SCI. In particular, it will clarify the acute and long-term effects of intervention intensity and elucidate a potential underlying cellular mechanism for these effects. Finally, it will further delineate the intervention parameters that maximize functional recovery, and promote the development of the most effective rehabilitation interventions following neurological injury.