Pharmacotherapy and passive exercise induce cortical reorganization independent of the order administered to spinalized rats

Following complete spinal cord injury (SCI), total sensorimotor paralysis occurs below the lesion site. Pharmacologic and rehabilitative treatments have been developed in attempts to restore locomotion following SCI, however the role of order of therapy administration has been largely neglected. We investigated the role of order of therapy administration in adult spinally transected rats on both open field locomotor performance and sensorimotor cortical reorganization using acute, multiple, single-neuron mapping techniques.Our hypothesis was that the interventions acted synergistically so that animals receiving the high dose of drug prior to exercise would have the highest proportion of responding cells and BBB scores based on previous results from our laboratory. Thus, adult Sprague Dawley rats were subjected to mid-thoracic (T9) spinal transection and then randomly placed into one of five therapy groups for an 8-week combination therapy regimen. Four of these groups received experimental combination pharmacotherapy and passive exercise in varied order, while the injured control group received sham treatments. Locomotor recovery was assessed at three points during the therapy regimen using the BBB locomotor rating scale representing the initial phase of recovery off-drug, the final phase of recovery on-drug and the final phase of recovery off-drug. Following the conclusion of the 8-week therapy regimen, the animals were anesthetized and cortical organization was assessed by quantifying the proportion of cells in the hindlimb rrepresentation of the somatosensory cortex that responded to tactile stimulation of the forelimbs.In accordance to previous results from our laboratory, BBB scores improved throughout the therapy regimen. However contrary to what we expected, there were no differences amongst the five therapy groups in terms of BBB scores for the final on-drug or the final off-drug tests. Additionally, there were overall differences in the proportion of responding cells across the five groups, but there were no differences in the proportion of responding cells between animals that received bike first versus drug first, or those that received the high dose versus low dose. As expected, each experimental group had a higher proportion of responding cells than did the control group. Finally, the extent of recovery was positively associated with cortical plasticity, matching our expectations. These data suggest that pharmacotherapy and passive exercise appear to have additive, independent effects on cortical reorganization following complete SCI, regardless of their order of administration.M.S., Biomedical Engineering -- Drexel University, 201