Multisystem neurorehabilitation in rodents with spinal cord injury

Abstract

A number of neurorehabilitative strategies have demonstrated efficacy in enhancing the recovery of sensorimotor function after a spinal cord injury (SCI). Combinations of task-specific motor training, epidural electrical stimulation of the spinal cord, and pharmacological interventions such as the administration of serotonergic agonists have resulted in remarkable improvements of locomotor and/or postural functions in rats with a complete SCI. Similar results are emerging in human patients with severe spinal cord damage. Synergistic amelioration of the loss of sensorimotor function through combinatorial approaches, i.e., the use of two or more interventions simultaneously, indicates that individual interventions can have both specific and complementary influences. For example, electrical stimulation applied at distinct rostrocaudal locations or agonists to specific receptor subtypes administered systemically tune unique aspects of locomotor movements. When administered simultaneously, the effects of these interventions can combine synergistically and result in significantly greater improvements in locomotor performance than either intervention alone. In addition, the use of robotic assistance during motor training, in particular in an “assist-as-needed” mode that allows a normal amount of variability in performing the task as opposed to a repetitive rigid training mode, can strongly enhance the effect of locomotor rehabilitation. We suggest that all of these interventions are enabling factors. They enable spinal neural circuitries to interpret task-specific sensory input and use this information in a feedforward manner to produce appropriate motor responses. Continued advancement in the development and refinement of such neurorehabilitative interventions will ensure progress toward improving the quality of life of individuals with a SCI or other severe sensorimotor dysfunctions.