IMR Press / JIN / Volume 22 / Issue 3 / DOI: 10.31083/j.jin2203071
Open Access Original Research
Chronic Stimulation Improves Motor Performance in an Ambulatory Rat Model of Spinal Cord Injury
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1 Bioengineering Program, University of Kansas, Lawrence, KS 66045, USA
2 Landon Center on Aging, University of Kansas Medical Center, Kansas City, KS 66160, USA
3 Neurosurgery, University of Kansas Medical Center, Kansas City, KS 66160, USA
4 Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA
5 Rehabilitation Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA
*Correspondence: (Shawn B. Frost)
J. Integr. Neurosci. 2023, 22(3), 71;
Submitted: 1 August 2022 | Revised: 27 November 2022 | Accepted: 30 November 2022 | Published: 15 May 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: The purpose of this proof-of-concept feasibility study was to determine if spike-triggered intraspinal microstimulation (ISMS), a form of activity dependent stimulation (ADS), results in improved motor performance in an ambulatory rat model of spinal cord injury (SCI). Methods: Experiments were carried out in adult male Sprague Dawley rats with moderate thoracic contusion injury. Rats were assigned to one of two groups: Control or ADS therapy. Four weeks post-SCI, all rats were implanted with a recording microelectrode in the left hindlimb motor cortex and a fine-wire stimulating electrode in the contralateral lumbar spinal cord. ADS was administered for 4 hours/day, 4 days/week, for 4 weeks. During therapy sessions, single-unit spikes were discriminated in real time in the hindlimb motor cortex and used to trigger stimulation in the spinal cord ventral horn. Control rats were similarly implanted with electrodes but did not receive stimulation therapy. Results: Motor performances of each rat were evaluated before SCI contusion, once a week post-SCI for four weeks (prior to electrode implantation), and once a week post-conditioning for four weeks. Basso, Beattie, and Bresnahan (BBB) locomotor scores were significantly improved in ADS rats compared to Control rats at 1 and 2 weeks after initiation of therapy. Foot fault scores on the Horizontal Ladder were significantly improved in ADS rats compared to pre-therapy ADS and Control rats after 1 week of therapy and recovered to near pre-injury scores after 3 weeks of therapy. The Ledged Beam test showed deficits after SCI in both ADS and Control rats but there were no significant differences between groups after 4 weeks of ADS therapy. Conclusions: These results show that chronic stimulation after spinal cord injury using a methodology of spike-triggered ISMS enhances behavioral recovery of locomotor function as measured by the BBB score and the Horizontal Ladder task. However, it is still uncertain if the behavioral improvements seen were dependent on spike-triggered ISMS.

activity dependent stimulation
spinal cord injury
spike-triggered intraspinal microstimulation
#3068/Paralyzed Veterans of America Research Foundation
NIH/NINDS R01 NS030853/Ronald D. Deffenbaugh Family Foundation
NIH/NINDS F31 NS105442/T32 Neurological Rehabilitation Sciences Training Program
Fig. 1.
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