Andre G Machado1, Jessica Cooperrider, Havan T Furmaga, Kenneth B Baker, Hyun-Joo Park, Zhihong Chen, John T Gale. 1. *Center for Neurological Restoration, Department of Neurosurgery, Neurological Institute, Cleveland Clinic, Cleveland, Ohio; ‡Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; §Department of Neurology, University of Minnesota, Minneapolis, Minnesota.
Abstract
BACKGROUND: Over 500,000 Americans have strokes every year, making stroke the leading cause for disability in the United States and in the industrialized world. New treatments to improve poststroke motor recovery are needed. OBJECTIVE: To investigate a novel approach for enhancing motor recovery that involves chronic, electrical stimulation of ascending cerebellar output combined with motor training. METHODS: Adult Sprague-Dawley rats underwent unilateral endothelin-1 injections in the dominant cerebral cortex and placement of a chronic stimulating electrode in the contralateral lateral cerebellar nucleus. After 1 week, the animals were separated into 2 groups (STIM+ and STIM-), matched for poststroke motor performance in the pasta matrix task. At 2 weeks post-ischemia, the treatment phase was initiated, with animals in the STIM+ group receiving pulsed, 30-Hz stimulation for 12 hours/day. Motor training continued for both groups over 3 to 5 weeks. RESULTS: A total of 23 animals were examined after 3 weeks of treatment. STIM+ animals showed a significant improvement in motor function compared with post-ischemia baseline performance as well as in comparison with the STIM- group. Immunohistochemistry revealed a significant increase in the perilesional expression of synaptophysin for the STIM+ vs the STIM- animals. CONCLUSION: These results indicate that chronic activation of ascending cerebellofugal pathways enhances motor recovery after focal cortical ischemia. The recovery was associated with an increase in perilesional cortical plasticity relative to nontreated controls.
BACKGROUND: Over 500,000 Americans have strokes every year, making stroke the leading cause for disability in the United States and in the industrialized world. New treatments to improve poststroke motor recovery are needed. OBJECTIVE: To investigate a novel approach for enhancing motor recovery that involves chronic, electrical stimulation of ascending cerebellar output combined with motor training. METHODS: Adult Sprague-Dawley rats underwent unilateral endothelin-1 injections in the dominant cerebral cortex and placement of a chronic stimulating electrode in the contralateral lateral cerebellar nucleus. After 1 week, the animals were separated into 2 groups (STIM+ and STIM-), matched for poststroke motor performance in the pasta matrix task. At 2 weeks post-ischemia, the treatment phase was initiated, with animals in the STIM+ group receiving pulsed, 30-Hz stimulation for 12 hours/day. Motor training continued for both groups over 3 to 5 weeks. RESULTS: A total of 23 animals were examined after 3 weeks of treatment. STIM+ animals showed a significant improvement in motor function compared with post-ischemia baseline performance as well as in comparison with the STIM- group. Immunohistochemistry revealed a significant increase in the perilesional expression of synaptophysin for the STIM+ vs the STIM- animals. CONCLUSION: These results indicate that chronic activation of ascending cerebellofugal pathways enhances motor recovery after focal cortical ischemia. The recovery was associated with an increase in perilesional cortical plasticity relative to nontreated controls.
Authors: Jessica Cooperrider; Havan Furmaga; Ela Plow; Hyun-Joo Park; Zhihong Chen; Grahame Kidd; Kenneth B Baker; John T Gale; Andre G Machado Journal: J Neurosci Date: 2014-07-02 Impact factor: 6.167
Authors: Elise Gondard; Lucy Teves; Lihua Wang; Chris McKinnon; Clement Hamani; Suneil K Kalia; Peter L Carlen; Michael Tymianski; Andres M Lozano Journal: J Neurosci Date: 2019-01-29 Impact factor: 6.167
Authors: Jessica Cooperrider; John T Gale; Raghavan Gopalakrishnan; Hugh H Chan; Connor Wathen; Hyun-Joo Park; Kenneth B Baker; Aasef G Shaikh; Andre G Machado Journal: Exp Neurol Date: 2015-12-14 Impact factor: 5.330
Authors: Jessica Cooperrider; Hugh H Chan; John T Gale; Hyun-Joo Park; Kenneth B Baker; Andre G Machado Journal: Neurosci Lett Date: 2019-03-07 Impact factor: 3.046
Authors: Sergiy Chornyy; Aniruddha Das; Julie A Borovicka; Davina Patel; Hugh H Chan; John K Hermann; Thomas C Jaramillo; Andre G Machado; Kenneth B Baker; Hod Dana Journal: Biomed Opt Express Date: 2021-07-16 Impact factor: 3.732
Authors: Hyun-Joo Park; Havan Furmaga; Jessica Cooperrider; John T Gale; Kenneth B Baker; Andre G Machado Journal: Brain Stimul Date: 2015-07-08 Impact factor: 8.955