Abstract T MP19: Optogenetic Stimulation of Cerebellar Dentate Nucleus Promotes Persistent Functional Recovery After Stroke
Objective: Functional recovery after stroke has been observed in both human and animal studies. Post-stroke brain stimulations are promising neurorestorative techniques as they allow direct manipulation of the target area’s excitability. Previously we have demonstrated that optogenetic neuronal stimulation of the ipsilesional primary motor cortex promotes functional recovery. To determine an optimal brain stimulation target, we test whether optogenetic neuronal stimulation of the contralesional cerebellar dentate nucleus (cLCN) can promote recovery. We hypothesize that stimulation of cLCN may be more effective, as it sends excitatory outputs to multiple motor and premotor areas.
Methods: Thy-1-ChR2-YFP line-18 transgenic male mice were used. Mice underwent stereotaxic surgery to implant a fiber cannula in cLCN, followed by an intraluminal middle cerebral artery suture occlusion. Three groups of mice were used: control non-stimulated stroke mice, short stim stimulated stroke mice (day5-14 post-stroke) and long stim stimulated stroke mice (day5-28 post-stroke). Sensorimotor behavior tests (rotating beam tests) were used to assess their recovery at day 0, 4, 7, 10, 14, 21 and 28 post-stroke.
Results: Our data showed that stimulated stroke mice recovered quickly, with significant improvement in distance traveled as early as day7 (p<0.05), and faster speed at day14 post-stroke (p<0.001). To evaluate whether the effect of cLCN stimulation was persistent, we tested the effects of short stim (day5-14) and long stim (day5-28) on recovery. Interestingly, the short stim group continued to recover after day14 without further stimulations and the long stim group did not further enhance recovery, indicating that functional outcome of cLCN stimulation is persistent, and prolonged stimulations may not be necessary to achieve permanent recovery. Analysis of pCREB activation showed that cLCN stimulation activates the dentatothalamocortical pathway.
Conclusion: Our data suggest that cLCN stimulations post-stroke can promote functional recovery, and this pro-recovery effect is persistent. Current studies examine the mechanisms of cLCN-induced recovery, including cortical excitability and synaptic/plasticity markers.
Author Disclosures: M.Y. Cheng: None. A.M. Shah: None. E.H. Wang: None. S. Ishizaka: None. A.R. Bautista: None. G. Sun: None. G.K. Steinberg: Consultant/Advisory Board; Modest; Medtronic. Research Grant; Significant; NIH NINDS, CIRM.
- © 2015 by American Heart Association, Inc.