Spinal electro - magnetic stimulation combined with transgene delivery of neurotrophin NT - 3 and 1 exercise : novel combination therapy for spinal contusion injury

21 Our recent terminal experiments revealed that administration of a single train of repetitive 22 spinal electro-magnetic stimulation (sEMS; 35 min) enhanced synaptic plasticity in spinal 23 circuitry following lateral hemisection SCI. In the current study, we have examined effects of 24 repetitive sEMS applied as a single train and chronically (5 weeks every other day) following 25 thoracic T10 contusion. Chronic studies involved examination of systematic sEMS 26 administration alone and combined with exercise training and transgene delivery of neurotrophin 27 NT-3 (adeno-associated virus AAV10-NT3). Electrophysiological intracellular/extracellular 28 recordings, immunohistochemistry, behavioral testing and anatomical tracing were performed to 29 assess effects of treatments. We found that administration of a single sEMS train induced 30 transient facilitation of transmission through preserved lateral white matter to motoneurons and 31 hindlimb muscles in chronically contused rats with effects lasting for at least 2 hours. These 32 physiological changes associated with increased immunoreactivity of GluR1 and GluR2/3 33 glutamate receptors in lumbar neurons. Systematic administration of sEMS alone for 5 weeks, 34 however, was unable to induce cumulative improvements of transmission in spino-muscular 35 circuitry or improve impaired motor function following thoracic contusion. Encouragingly, 36 chronic administration of sEMS followed by exercise training (running in exercise ball and 37 swimming) induced: (i) sustained strengthening of transmission to lumbar motoneurons and 38 hindlimb muscles, (ii) better retrograde transport of anatomical tracer and (iii) improved 39 locomotor function. Greatest improvements were seen in the group that received exercise 40 combined with sEMS and AAV-NT3. 41