Steinbeis experts develop stimulator for researching Parkinson’s through animal experimentation
Parkinson’s disease is a disorder of the brain that leads to the progressive degeneration of nerve cells. A relatively new procedure called deep brain stimulation (DBS) involves sending electrical impulses to a small region of the brain below the cerebral cortex, which, among other things, is responsible for the subconscious control of voluntary muscles. Recent developments make it possible to use DBS to treat the symptoms of Parkinson’s during early stages of the condition. Despite the recent medical success of DBS, there is still speculation regarding its exact mechanisms, such that until now it has only been possible to make empirical improvements in therapy. As part of an alliance with the professorial chair for biophysics at University Medical Center Rostock and Rückmann und Arndt from Berlin, the Steinbeis Transfer Center for Cell Manipulation and Monitoring Systems (CMMS) has now developed a stimulation board and stimulation electrodes that make it possible to conduct long-term DBS studies.
Treating advanced Parkinson’s disease originally involved lesion surgery. This destroyed a core area of the thalamus in the division of the forebrain called the diencephalon. This alleviated the symptoms of the disease, mainly by interrupting faulty “connections” caused by the progressive loss of black nerve substance. To locate the optimal area for the lesion during surgery, doctors used a stimulation electrode. The positive impact of this electrical stimulation was already noticeable during operations, leading to the idea that a DBS therapy could be developed. One unusual feature of this process was that an operating technique had been discovered for humans without prior experimentation involving a suitable animal model.
Because systematic invasive examinations are forbidden on humans for ethical reasons and cell-based in vitro methods are unfortunately unable to reflect the complexity of this particular clinical condition, there is currently no other way to conduct research into the neuronal mechanisms of DBS and its optimization than to use animal models, such as rats. However, the difference in the size of the brain of a rat and a human being means that the stimulation conditions of clinical treatment cannot be compared like for like with animal models. In order to achieve meaningful results from testing nevertheless, the professorial chair of biophysics at University Medical Center Rostock has been working with Rückmann und Arndt and the Steinbeis Transfer Center for Cell Manipulation and Monitoring Systems (CMMS), which is also based in Rostock, on the development and testing of electrodes and stimulators specially matched to the anatomy of rats. The advantage offered by these mobile stimulators is that they make it possible for the first time to conduct representative long-term studies on animals, which are completely free to move around for up to six weeks or more under continual stimulation. In human terms, this is the equivalent to a trial period under continual stimulation of approximately 4.5 years. This overcomes the limitations of previous animal studies due to equipment, such as obstructive external cable harnesses.
Animal experimentation at the Clinic and Polyclinic for Neurology at University Medical Center Rostock involves inducing a one-sided socalled hemi-Parkinson condition. This makes it possible to test motor functions by comparing the healthy and the diseased sides of the brain. The stimulation electrodes are implanted in the subthalamic nucleus of the diseased side. Parallel testing also has to be performed on healthy, sham-lesioned and sham-DBS treated animals. To study the long-term effects of DBS on the sensorimotor functions and emotions, the behavior of the chronically instrumented mobile hemi-Parkinson rats is examined at different times during the course of the condition.
The project team working with the Steinbeis researchers successfully demonstrated significant lesion and therapy impacts during the behavior tests with the new system. The model thus constitutes an adaptable platform for testing different stimulation parameters, such as new types of electrodes or other, unexplored areas of interest. Stable chronic instrumentation is also suitable for further animal models of diseases in which clinical DBS may prove successful. In addition to motor disorders for which DBS approval has already been gained, such as Parkinson’s disease, dystonia, and essential tremor, there are other indications DBS could be used on in the future, such as obsessive-compulsive disorders.
References
- Badstübner, K., Gimsa, U., Weber, I., Tuchscherer, A., Gimsa, J. (2017). Deep brain stimulation of hemiparkinsonian rats with unipolar and bipolar electrodes for up to 6 weeks: behavioral testing of freely moving animals. Parkinson’s Dis. Article ID: 5693589, 1-18.
- Badstübner, K., Stubbe, M., Kröger, T., Mix, E., Gimsa, J. (2017). Impedance detection of the electrical resistivity of the wound tissue around deep brain stimulation electrodes permits registration of the encapsulation process in a rat model. J. Electr. Bioimp. 8, 11-24.
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Contact
Prof. Dr. habil. Jan Gimsa
Steinbeis Transfer Center Cell Manipulation and Monitoring Systems (CMMS) (Rostock
Dr. Kathrin Badstübner
University Medical Center Rostock, Hospital and Polyclinic for Neurology (Rostock)
Dr. Robert Arndt
Rückmann und Arndt GbR (Berlin)