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Chronic 30-Hz Deep Cerebellar Stimulation Coupled With Training Enhances Post-ischemia Motor Recovery and Peri-infarct Synaptophysin Expression in Rodents

Machado, Andre G. MD, PhD*,‡; Cooperrider, Jessica MS*,‡; Furmaga, Havan T. PhD*,‡; Baker, Kenneth B. PhD§; Park, Hyun-Joo PhD; Chen, Zhihong PhD; Gale, John T. PhD*,‡

doi: 10.1227/

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.

ABBREVIATIONS: CCD, crossed cerebellar diaschisis

ET-1, endothelin-1

LCN, lateral cerebellar nucleus

SEM, standard error of the mean

*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

Correspondence: Andre Machado, MD, PhD, Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, 9500 Euclid Ave, S31, Cleveland, OH 44195. E-mail:

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Received November 14, 2012

Accepted April 23, 2013

Copyright © by the Congress of Neurological Surgeons