Article
Comparing behavioral effects in short-term DBS vs. long-term DBS in an animal model
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Authors
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D. Meinhard
- Abteilung für Stereotaxie und funktionelle Neurochirurgie, Neurochirurgische Klinik, Universitätsklinik Düsseldorf
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M. Pum
- Institut für experimentelle Psychologie, Universitätsklinikum Düsseldorf
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D. Harnack
- Klinik für Neurologie, Charité - Universitätsmedizin Berlin
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J. Huston
- Institut für experimentelle Psychologie, Universitätsklinikum Düsseldorf
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J. Vesper
- Abteilung für Stereotaxie und funktionelle Neurochirurgie, Neurochirurgische Klinik, Universitätsklinik Düsseldorf
| Published: | April 28, 2011 |
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Outline
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Objective: Chronic high-frequency deep brain stimulation (cDBS) of the subthalamic nucleus (STN) is an established and reliable treatment option for Parkinson’s disease (PD). The effects of DBS in PD patients have been modelled in the 6-hydroxydopamine (6-OHDA) animal model of PD. It was shown that the motor symptoms expressed by rats with unilateral 6-OHDA lesions of the nigrostriatal tract like rotational behavior, impaired rotarod, impaired movement initiation, or impaired gait, could be attenuated by short-term DBS (stDBS; 5–60 min). There may be substantial functional differences between stDBS of the STN as applied in most preclinical animal studies and the use of cDBS as performed in PD patients. Therefore, we established an animal model to investigate the behavioral effects of cDBS of the STN and to compare them with the effects of short-term DBS (60 min), as it is commonly used.
Methods: For chronic deep brain stimulation, rats that had been subjected to unilateral 6-OHDA lesions of the medial forebrain bundle were implanted with an electrode aimed at the STN on the lesioned side. The stimulator (experimental group) or a size- and weight-adapted dummy (control group) were implanted subcutaneously and connected to the stimulating electrode. A week following the implantation of the stimulating, the first testing was conducted. The animals were repeatedly tested over 3 weeks for turning behavior, behavior on the rotarod, forepaw use during wall-supported rearing, and movement-initiation during the stepping test.
Results: Testing showed significant improvement on turning behavior, behavior on the rotarod and the initiation of movement during the stepping test in both groups one week after implanting the electrodes. The results differed during long-term testing. In the control group, the improvement effects vanished completely after 2 weeks but in the experimental group, the improvement effects were consistent.
Conclusions: Testing showed significant, consistent improvement in behavioral aspects under cDBS. This effect of initial improvement and declining of the effects can also be seen in patients suffering from PD undergoing DBS, and is well-known as placement effect. We were able to show the placement effects in an animal model. The mechanism behind this placement effect remains to be investigated in further experiments.
