This title appears in the Scientific Report : 2021 
Towards chronic deep brain stimulation in freely moving hemiparkinsonian rats: applicability and functionality of a fully implantable stimulation system
Apetz, Nadine (Corresponding author)
Paralikar, Kunal / Neumaier, Bernd / Drzezga, Alexander / Wiedermann, Dirk / Iyer, Rajesh / Munns, Gordon / Scott, Erik / Timmermann, Lars / Endepols, Heike
Molekulare Organisation des Gehirns; INM-2
Nuklearchemie; INM-5
Journal of neural engineering, 18 (2021) 3, S. 036018
Bristol Institute of Physics Publishing 2021
10.1088/1741-2552/abe806
Journal Article
Decoding Brain Organization and Dysfunction
Restricted
Published on 2021-03-16. Available in OpenAccess from 2022-03-16.
Please use the identifier: http://hdl.handle.net/2128/27970 in citations.
Please use the identifier: http://dx.doi.org/10.1088/1741-2552/abe806 in citations.


This study aimed at investigating a novel fully implantable deep brain stimulation(DBS) system and its ability to modulate brain metabolism and behavior through subthalamicnucleus (STN) stimulation in a hemiparkinsonian rat model.Approach.Twelve male rats wereunilaterally lesioned with 6-hydroxydopamine in the medial forebrain bundle and received a fullyimplantable DBS system aiming at the ipsilesional STN. Each rat underwent three cylinder tests toanalyze front paw use: a PRE test before any surgical intervention, an OFF test after surgery butbefore stimulation onset and an ON test under DBS. To visualize brain glucose metabolism in theawake animal, two [18F]FDG scans were conducted in the OFF and ON condition. At least 4 weeksafter surgery, an [18F]FDOPA scan was used to check for dopaminergic integrity.Main results.Ingeneral, STN DBS increased [18F]FDG uptake ipsilesionally and decreased it contralesionally. Morespecifically, bilateral orbitofrontal cortex, ipsilateral caudate putamen, sensorimotor cortex andnucleus accumbens showed significantly higher tracer uptake in ON compared to OFF condition.Contralateral cingulate and secondary motor cortex, caudate putamen, amygdala, hippocampus,retrosplenial granular cortex, superior colliculus, and parts of the cerebellum exhibitedsignificantly higher [18F]FDG uptake in the OFF condition. On the behavioral level, stimulationwas able improve use of the contralesional affected front paw suggesting an effective stimulationproduced by the implanted system.Significance.The fully implantable stimulation systemdeveloped by us and presented here offers the output of arbitrary user-defined waveforms, patternsand stimulation settings and allows tracer accumulation in freely moving animals. It is therefore asuitable device for implementing behavioral PET studies. It contributes immensely to thepossibilities to characterize and unveil the effects and mechanisms of DBS offering valuable cluesfor future improvements of this therapy