INTRODUCTION: Poststroke brain stimulations are promising neurorestorative techniques because they allow direct manipulation of the target area's excitability. Previously, we demonstrated that optogenetic neuronal stimulation of the ipsilesional primary motor cortex promotes functional recovery. To determine an optimal brain stimulation target, we tested whether optogenetic neuronal stimulation of the contralesional cerebellar dentate nucleus (cDN) can promote recovery. We hypothesized that stimulation of cDN may be more effective, because it sends excitatory outputs to multiple cerebral regions. METHODS: Thy-1-ChR2-YFP line-18 @entity19 underwent stereotaxic fiber cannula implant in cDN, followed by transient @entity2500 . Control nonstimulated @entity19 , short-term stimulated @entity19 (day 5-14) and long-term stimulated @entity19 (day 5-28) were used. Sensorimotor behavior tests were used to assess their recovery at day 0, 4, 7, 10, 14, 21, and 28 poststroke. @entity19 were euthanized at various time points for immunohistochemistry and Western blots. RESULTS: Our data showed that stimulated @entity64 @entity19 recovered with significant improvement in distance traveled (P < .01) and faster speed on the rotating beam at day 14 poststroke (P < .05). The short-term simulation group continued to recover after day 14 without further stimulations and the long-term stimulation group did not show additional enhanced recovery, indicating that the functional outcome of cDN stimulation is persistent. Western blotting showed that stimulated @entity64 @entity19 exhibited a significant decrease in pCREB and total @entity15983 expression in ipsilesional M1 (P < .01) and an increase in @entity22262 expression in ipsilesional S1 (P < .05). CONCLUSION: Our data suggest that cDN stimulations poststroke can promote functional recovery and this prorecovery effect is persistent. Recovery of cDN-stimulated @entity64 @entity19 is associated with upregulation of plasticity marker @entity22262 and downregulation of @entity15983 signaling. Current studies examine the effects of cDN stimulations on axonal sprouting and the contribution of @entity15983 in recovery. cDN could be a promising brain stimulation target for @entity64 recovery.

161   Optogenetic Stimulation of Cerebellar Dentate Nucleus Promotes Persistent Functional Recovery After XXXX .

@entity64 :: ('MESH:D020521', 'Disease') :: ['stroke'] @entity19 :: ('10090', 'Species') :: ['mice', 'transgenic mice', 'Mice'] @entity2500 :: ('MESH:D020244', 'Disease') :: ['middle cerebral artery occlusion'] @entity15983 :: ('12912(Tax:10090)', 'Gene') :: ['CREB'] @entity22262 :: ('14432(Tax:10090)', 'Gene') :: ['GAP43']
@entity64 :: (MESH:D020521,Disease) :: ['Stroke']
