title: Spinal electro-magnetic stimulation combined with transgene delivery of neurotrophin NT-3 and exercise: novel combination therapy for spinal contusion injury.
abstract: Our recent terminal experiments revealed that administration of a single train of repetitive spinal electromagnetic stimulation (sEMS; 35 min) enhanced synaptic plasticity in spinal circuitry following lateral hemisection spinal cord injury. In the current study, we have examined effects of repetitive sEMS applied as a single train and chronically (5 wk, every other day) following thoracic T10 contusion. Chronic studies involved examination of systematic sEMS administration alone and combined with exercise training and transgene delivery of neurotrophin [adeno-associated virus 10-neurotrophin 3 (AAV10-NT3)]. Electrophysiological intracellular/extracellular recordings, immunohistochemistry, behavioral testing, and anatomical tracing were performed to assess effects of treatments. We found that administration of a single sEMS train induced transient facilitation of transmission through preserved lateral white matter to motoneurons and hindlimb muscles in chronically contused rats with effects lasting for at least 2 h. These physiological changes associated with increased immunoreactivity of GluR1 and GluR2/3 glutamate receptors in lumbar neurons. Systematic administration of sEMS alone for 5 wk, however, was unable to induce cumulative improvements of transmission in spinomuscular circuitry or improve impaired motor function following thoracic contusion. Encouragingly, chronic administration of sEMS, followed by exercise training (running in an exercise ball and swimming), induced the following: 1) sustained strengthening of transmission to lumbar motoneurons and hindlimb muscles, 2) better retrograde transport of anatomical tracer, and 3) improved locomotor function. Greatest improvements were seen in the group that received exercise combined with sEMS and AAV-NT3.
authors.affiliation: Northport Veterans Affairs Medical Center, Northport, New York; Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, New York; and.
authors.forename: Hayk A
authors.initials: HA
authors.lastname: Petrosyan
authors.affiliation: Northport Veterans Affairs Medical Center, Northport, New York; Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, New York; and.
authors.forename: Valentina
authors.initials: V
authors.lastname: Alessi
authors.affiliation: Northport Veterans Affairs Medical Center, Northport, New York;
authors.forename: Arsen S
authors.initials: AS
authors.lastname: Hunanyan
authors.affiliation: Department of Physical Therapy, Division of Rehabilitation Sciences, Stony Brook University, Stony Brook, New York.
authors.forename: Sue A
authors.initials: SA
authors.lastname: Sisto
authors.affiliation: Northport Veterans Affairs Medical Center, Northport, New York; Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, New York; and victor.arvanian@stonybrook.edu.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Arvanian
mesh_terms: D000818:Animals; D003131:Combined Modality Therapy; D000229:Dependovirus / Q000502:physiology; D019054:Evoked Potentials, Motor; D005081:Exercise Therapy; D005260:Female; D005822:Genetic Vectors / Q000627:therapeutic use*; D006614:Hindlimb / Q000503:physiopathology; D055909:Magnetic Field Therapy / Q000379:methods*; D059346:Magnets; D009043:Motor Activity; D009046:Motor Neurons / Q000502:physiology; D018482:Muscle, Skeletal / Q000503:physiopathology; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D020933:Neurotrophin 3 / Q000235:genetics / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000503:physiopathology* / Q000628:therapy* / Q000821:virology; D019076:Transgenes
chemical_list: D020933:Neurotrophin 3; D017470:Receptors, Glutamate
keywords: AAV; exercise; magnetic stimulation; spinal cord injury