Artikel
Chronic deep brain stimulation of the entopeduncular nucleus or the centromedian-parafascicular complex in the rat 6-hydroxydopamine Parkinson model improves levodopa-induced dyskinesias
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Veröffentlicht: | 28. April 2011 |
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Gliederung
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Objective: Deep brain stimulation (DBS) is used in Parkinson's disease (PD) to treat levodopa-induced dyskinesias and fluctuations. The subthalamic nucleus (STN) and the globus pallidus internus (GPi) have been the standard targets in men. More recently, the centermedian-parafascicular complex (CM-Pf) has also been discussed as a possible target for DBS. We studied the effects of chronic DBS of the CM-Pf and the entopeduncular nucleus (EPN, the rat equivalent to the human GPi) on levodopa-induced dyskinesias in the 6-hydroxydopamine (6-OHDA) rat model of PD.
Methods: Unilateral nigrostriatal lesions were induced by injection of 6-OHDA in the medial forebrain bundle of female Sprague-Dawley rats (n=14). Subsequently, these rats were rendered dyskinetic by regular intraperitoneal injections of levodopa. Ipsilateral to the lesion, bipolar electrodes for stimulation were implanted in the EPN and the CM-Pf. In addition, electrodes were implanted in the dorsolateral striatum for the recording of local field potentials (LFPs). After recovery, individual thresholds for side effects of stimulation were determined. Thereafter, EPN, CM-Pf or sham DBS was applied for five days (130Hz, 80µs) and the effects of DBS on levodopa-induced dyskinesias were assessed.
Results: Both EPN and CM-Pf DBS improved dyskinesias (one-way ANOVA followed by Tukey test, p < 0.05). LFP activity in the beta frequency band was reduced after the injection of levodopa (two-way ANOVA followed by Tukey test, p < 0.05), while EPN and CM-Pf stimulation had no effect on beta oscillations.
Conclusions: Our results show that DBS of the EPN and CM-Pf might be useful to treat dyskinesias. Furthermore, we could demonstrate that DBS of either target exerts its therapeutic effect in the 6-OHDA rat model independent from its effect on beta activity.