Experimental deep brain stimulation in animal models.
DEEP BRAIN STIMULATION (DBS) as a therapy in neurological and psychiatric disorders is widely applied in the field of functional and stereotactic neurosurgery. In this respect, experimental DBS in animal models is performed to evaluate new indications and new technology. In this article, we review our experience with the concept of experimental DBS, including its development and validation. An electrode construction was developed using clinical principles to perform DBS unilaterally or bilaterally in freely moving rats. The stimulation parameters were adjusted for the rat using current density calculations. We performed validation studies in 2 animal models: a rat model of Parkinson's disease (bilateral 6-hydroxydopamine infusion in the striatum) and a rat model of Huntington's disease (transgenic rats). The effects of DBS were evaluated in different behavioral tasks measuring motor and cognitive functions. The electrode construction developed allows experimental DBS to be performed in freely moving rats. With the current setup, electrodes are placed in the target in 70% to 95% of the cases. Using a rat model, we showed that bilateral DBS of the subthalamic nucleus improves parkinsonian motor disability, but can induce behavioral side effects, similar to the clinical situation. In addition, we showed that DBS of the globus pallidus can improve motor and cognitive symptoms in a rat model of Huntington's disease. Nevertheless, during the process of the development and validation of experimental DBS, we encountered specific problems. These are discussed in detail. Experimental DBS in freely moving animals is an adequate tool to explore new indications for DBS and to refine DBS technology.
Tan
Sonny Kh
SKh
Department of Neuroscience, Maastricht University, Department of Neurosurgery, Maastricht University Medical Center, European Graduate School of Neuroscience (EURON), Maastricht Institute of Neuromodulative Development (MIND), Maastricht, The Netherlands.
Vlamings
Rinske
R
Lim
Leewei
L
Sesia
Thibault
T
Janssen
Marcus Lf
ML
Steinbusch
Harry Wm
HW
Visser-Vandewalle
Veerle
V
Temel
Yasin
Y
D000818:Animals; D046690:Deep Brain Stimulation / Q000379:methods*; D004195:Disease Models, Animal; D004566:Electrodes; D009422:Nervous System Diseases / Q000628:therapy*; D051381:Rats; D015203:Reproducibility of Results