Chronic high-frequency stimulation (HFS) of the subthalamic nucleus (STN) protects nigral dopaminergic neurons from neurodegeneration in animal models of Parkinson's disease (PD). However, these data are challenged by the lack of control for neuroprotective effects that might be related to tissue damage due to electrode insertion or STN-HFS. Here we report the first placebo-controlled study on continuous STN-HFS in a rat model of PD using an implantable microstimulation system. We found a significant increase of preserved dopaminergic nigral neurons on the lesioned side (expressed as ratio to the non-lesioned side) of approximately 50% in comparison to STN sham-stimulated and STN-naive rats. These data provide evidence for the phenotypic rescue of nigral dopamine neurons by long-term STN-HFS in this animal model of PD.
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