Chronic Stimulation Improves Motor Performance in an Ambulatory Rat Model of Spinal Cord Injury
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: Experimen...
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| Format: | Article |
| Language: | English |
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IMR Press
2023-05-01
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| Series: | Journal of Integrative Neuroscience |
| Subjects: | |
| Online Access: | https://www.imrpress.com/journal/JIN/22/3/10.31083/j.jin2203071 |
| _version_ | 1797814480330031104 |
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| author | Jordan A. Borrell Domenico Gattozzi Dora Krizsan-Agbas Matthew W. Jaeschke Randolph J. Nudo Shawn B. Frost |
| author_facet | Jordan A. Borrell Domenico Gattozzi Dora Krizsan-Agbas Matthew W. Jaeschke Randolph J. Nudo Shawn B. Frost |
| author_sort | Jordan A. Borrell |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T08:08:21Z |
| format | Article |
| id | doaj.art-6afaeeafa8ca4a9e88106790a80167cb |
| institution | Directory Open Access Journal |
| issn | 0219-6352 |
| language | English |
| last_indexed | 2024-03-13T08:08:21Z |
| publishDate | 2023-05-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Journal of Integrative Neuroscience |
| spelling | doaj.art-6afaeeafa8ca4a9e88106790a80167cb2023-06-01T01:59:17ZengIMR PressJournal of Integrative Neuroscience0219-63522023-05-012237110.31083/j.jin2203071S0219-6352(22)00492-2Chronic Stimulation Improves Motor Performance in an Ambulatory Rat Model of Spinal Cord InjuryJordan A. Borrell0Domenico Gattozzi1Dora Krizsan-Agbas2Matthew W. Jaeschke3Randolph J. Nudo4Shawn B. Frost5Bioengineering Program, University of Kansas, Lawrence, KS 66045, USANeurosurgery, University of Kansas Medical Center, Kansas City, KS 66160, USAMolecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USABioengineering Program, University of Kansas, Lawrence, KS 66045, USALandon Center on Aging, University of Kansas Medical Center, Kansas City, KS 66160, USALandon Center on Aging, University of Kansas Medical Center, Kansas City, KS 66160, USABackground: 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.https://www.imrpress.com/journal/JIN/22/3/10.31083/j.jin2203071activity dependent stimulationneuromodulationspinal cord injuryclosed-loopspike-triggered intraspinal microstimulation |
| spellingShingle | Jordan A. Borrell Domenico Gattozzi Dora Krizsan-Agbas Matthew W. Jaeschke Randolph J. Nudo Shawn B. Frost Chronic Stimulation Improves Motor Performance in an Ambulatory Rat Model of Spinal Cord Injury Journal of Integrative Neuroscience activity dependent stimulation neuromodulation spinal cord injury closed-loop spike-triggered intraspinal microstimulation |
| title | Chronic Stimulation Improves Motor Performance in an Ambulatory Rat Model of Spinal Cord Injury |
| title_full | Chronic Stimulation Improves Motor Performance in an Ambulatory Rat Model of Spinal Cord Injury |
| title_fullStr | Chronic Stimulation Improves Motor Performance in an Ambulatory Rat Model of Spinal Cord Injury |
| title_full_unstemmed | Chronic Stimulation Improves Motor Performance in an Ambulatory Rat Model of Spinal Cord Injury |
| title_short | Chronic Stimulation Improves Motor Performance in an Ambulatory Rat Model of Spinal Cord Injury |
| title_sort | chronic stimulation improves motor performance in an ambulatory rat model of spinal cord injury |
| topic | activity dependent stimulation neuromodulation spinal cord injury closed-loop spike-triggered intraspinal microstimulation |
| url | https://www.imrpress.com/journal/JIN/22/3/10.31083/j.jin2203071 |
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