Chronic electrical stimulation of the contralesional lateral cerebellar nucleus enhances recovery of motor function after cerebral ischemia in rats
Andre G Machado, Kenneth B Baker, Daniel Schuster, Robert S Butler, Ali Rezai, Andre G Machado, Kenneth B Baker, Daniel Schuster, Robert S Butler, Ali Rezai
Abstract
Novel neurorehabilitative strategies are needed to improve motor outcomes following stroke. Based on the disynaptic excitatory projections of the dentatothalamocortical pathway to the motor cortex as well as to anterior and posterior cortical areas, we hypothesize that chronic electrical stimulation of the contralesional dentate (lateral cerebellar) nucleus output can enhance motor recovery after ischemia via augmentation of perilesional cortical excitability. Seventy-five Wistar rats were pre-trained in the Montoya staircase task and subsequently underwent left cerebral ischemia with the 3-vessel occlusion model. All survivors underwent stereotactic right lateral cerebellar nucleus (LCN) implantation of bipolar electrodes. Rats were then randomized to 4 groups: LCN stimulation at 10 pps, 20 pps, 50 pps or sham stimulation, which was delivered for a period of 6 weeks. Performance on the Montoya staircase task was re-assessed over the last 4 weeks of the stimulation period. On the right (contralesional) side, motor performance of the groups undergoing sham, 10 pps, 20 pps and 50 pps stimulation was, respectively, 2.5+/-2.7; 2.1+/-2.5; 6.0+/-3.9 (p<0.01) and 4.5+/-3.5 pellets. There was no difference on the left (ipsilesional) side motor performance among the sham or stimulation groups, varying from 15.9+/-6.7 to 17.2+/-2.1 pellets. We conclude that contralesional chronic electrical stimulation of the lateral cerebellar nucleus at 20 pps but not at 10 or 50 pps improves motor recovery in rats following ischemic strokes. This effect is likely to be mediated by increased perilesional cortical excitability via chronic activation of the dentatothalamocortical pathway.
Conflict of interest statement
Conflicts of Interest: Andre Machado has a significant conflict of interest related to this research with IntElect Medical due inventorship shares (stockholder), as a consultant and as a member of the scientific advisory board. Andre Machado is employed by the Cleveland Clinic. IntElect Medical is a spin-off company of the Cleveland Clinic.
Kenneth Baker has a conflict of interest with IntElect Medical due to inventorship shares. Dr. Baker is employed by the Cleveland Clinic. IntElect Medical is a spin-off company of the Cleveland Clinic.
Daniel Schuster has no conflicts with this research other than his employment at the Cleveland Clinic. Daniel Schuster is employed by the Cleveland Clinic. IntElect Medical is a spin-off company of the Cleveland Clinic.
Robert Butler has no conflicts with this research other than his employment at the Cleveland Clinic. Daniel Schuster is employed by the Cleveland Clinic. IntElect Medical is a spin-off company of the Cleveland Clinic.
Ali Rezai has significant conflict of interest related to this research with IntElect Medical. He has inventorship shares (stockholder). He was until 2008 the chairman of the scientific advisory board, a member of the IntElect Medical board and a consultant to the company. He no longer serves in these capacities. Dr. Rezai is employed by the Cleveland Clinic. IntElect Medical is a spin-off company of the Cleveland Clinic.
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Source: PubMed