Re-training locomotor circuitry in a rat model of SCI

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DESCRIPTION (provided by applicant): One of the most promising therapeutic strategies for spinal cord injury is weight-supported treadmill training. This rehabilitation therapy seeks to re-train the spinal cord circuitry below the level of injury to participate in functional locomotion. The mammalian spinal cord, humans included, contains complex neuronal circuitry that participates in the generation of the repeating pattern of motor activity (step-cycle) associated with normal over-ground locomotion. Both animal and human studies have demonstrated that moving the hindlimbs to mimic normal walking, usually on a treadmill with rehabilitation assistants, can lead to improved hindlimb locomotor function. However, the treadmill speed that is used is very slow compared to normal walking and much of the body weight of the animal or patient must be supported externally. Consequently, relatively few step-cycles are generated during a re-training session, certainly far fewer than normal walking. We hypothesized that a re-training strategy that allowed for many more step-cycles to be completed would be more effective and that re-training the locomotor circuitry would be much more successful. Some of the components that are thought to be important for the re-training process include step-cycle number, cutaneous feedback from the foot, limb position, and weight-bearing feedback from the leg. How each of these individual components contribute to successful rehabilitation, and the physiological and cellular mechanisms underlying the re-training process are not known. We have devised a strategy to use buoyancy during swimming to provide weight-support which allows for high numbers of step-cycles to be completed during a rehabilitation session. We have also incorporated a simple approach to provide phasic cutaneous feedback during swimming and partial limb-loading (weight- bearing) during walking in shallow water. We hope to uncover what relative contributions step-cycle number and frequency, cutaneous feedback and limb-loading make to the overall success of a locomotor rehabilitation strategy. In addition, we will begin to look at the mechanisms of rehabilitation associated plasticity using a custom made array to detect changes in mRNA levels in spinal cord tissue following different training protocols.