Microelectrode Clusters Enable Therapeutic Deep Brain Stimulation Without Noticeable Side-Effects in a Rodent Model of Parkinson's Disease.

Background: Deep Brain Stimulation (DBS) is an established treatment for motor symptoms in Parkinson's disease (PD). However, side effects often limit the usefulness of the treatment. New method: To mitigate this problem, we developed a novel cluster of ultrathin platinum-iridium microelectrodes (n = 16) embedded in a needle shaped gelatin vehicle. In an established rodent PD-model (6-OHDA unilateral lesion), the clusters were implanted in the subthalamic area for up to 8 weeks. In an open field setting, combinations of microelectrodes yielding therapeutic effects were identified using statistical methods. Immunofluorescence techniques were used for histological assessments of biocompatibility. Results: In all rats tested (n = 5), we found subsets of 3-4 microelectrodes which, upon stimulation (160 Hz, 60 mu s pulse width, 25-40 mu A/microelectrode), prompted normal movements without noticeable side effects. Other microelectrode subsets often caused side effects such as rotation, dyskinesia and tremor. The threshold (per microelectrode) to elicit normal movements strongly depended on the number of activated microelectrodes in the selected subset. The histological analysis revealed viable neurons close to the electrode contacts, minor microglial and astrocytic reactions and no major changes in the vasculature, indicating high biocompatibility. Comparison to existing methods and conclusion: By contrast to the continuous and relatively large stimulation fields produced by existing DBS electrodes, the developed microelectrode cluster enables a fine-tuned granular and individualized microstimulation. This granular type of stimulation pattern provided powerful and specific therapeutic effects, free of noticeable side effects, in a PD animal model.