Towards chronic deep brain stimulation in freely moving hemiparkinsonian rats: applicability and functionality of a fully implantable stimulation system
Towards chronic deep brain stimulation in freely moving hemiparkinsonian rats: applicability and functionality of a fully implantable stimulation system
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DOI：
10.1088/1741-2552/abe806
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发表时间：
2021-02
影响因子：
4
通讯作者：
N. Apetz;K. Paralikar;B. Neumaier;A. Drzezga;D. Wiedermann;Rajesh Iyer;Gordon Munns;Erik R. Scott;L. Timmermann;H. Endepols
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作者：
N. Apetz;K. Paralikar;B. Neumaier;A. Drzezga;D. Wiedermann;Rajesh Iyer;Gordon Munns;Erik R. Scott;L. Timmermann;H. Endepols
Objective.本研究旨在研究一种新型的完全植入式脑深部电刺激（DBS）系统及其通过刺激丘脑底核（DBS）调节偏侧帕金森病大鼠模型脑代谢和行为的能力。Approach. 12只雄性大鼠在内侧前脑束中用6-羟基多巴胺单侧损伤，并接受完全植入式DBS系统，目的是在同侧脑干。每只大鼠进行三次圆柱测试以分析前爪用途：在任何手术干预之前的PRE测试，在手术之后但在刺激开始之前的OFF测试和在DBS下的ON测试。为了可视化清醒动物的脑葡萄糖代谢，在OFF和ON条件下进行两次[18F]FDG扫描。手术后至少4周，使用[18F]FDOPA扫描检查多巴胺能完整性。主要结果。一般而言，DBS可增加同侧[18 F]FDG摄取，减少对侧摄取。更具体地说，双侧眶额皮质，同侧尾壳核，感觉运动皮质和核延髓显示出显着较高的示踪剂摄取ON相比，OFF条件。在OFF条件下，外侧扣带回和次级运动皮质、尾壳核、杏仁核、海马、压后颗粒皮质、上级丘和小脑部分显示出显著更高的[18 F]FDG摄取。在行为水平上，刺激能够改善对侧受影响前爪的使用，表明植入系统产生的有效刺激。意义我们开发的完全植入式刺激系统提供了任意用户定义的波形、模式和刺激设置的输出，并允许在自由移动的动物中积累示踪剂。因此，它是一个合适的设备进行行为PET研究。它极大地有助于表征和揭示DBS的作用和机制的可能性，为这种疗法的未来改进提供了有价值的线索。
Objective. This study aimed at investigating a novel fully implantable deep brain stimulation (DBS) system and its ability to modulate brain metabolism and behavior through subthalamic nucleus (STN) stimulation in a hemiparkinsonian rat model. Approach. Twelve male rats were unilaterally lesioned with 6-hydroxydopamine in the medial forebrain bundle and received a fully implantable DBS system aiming at the ipsilesional STN. Each rat underwent three cylinder tests to analyze front paw use: a PRE test before any surgical intervention, an OFF test after surgery but before stimulation onset and an ON test under DBS. To visualize brain glucose metabolism in the awake animal, two [18F]FDG scans were conducted in the OFF and ON condition. At least 4 weeks after surgery, an [18F]FDOPA scan was used to check for dopaminergic integrity. Main results. In general, STN DBS increased [18F]FDG uptake ipsilesionally and decreased it contralesionally. More specifically, bilateral orbitofrontal cortex, ipsilateral caudate putamen, sensorimotor cortex and nucleus 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 exhibited significantly higher [18F]FDG uptake in the OFF condition. On the behavioral level, stimulation was able improve use of the contralesional affected front paw suggesting an effective stimulation produced by the implanted system. Significance. The fully implantable stimulation system developed by us and presented here offers the output of arbitrary user-defined waveforms, patterns and stimulation settings and allows tracer accumulation in freely moving animals. It is therefore a suitable device for implementing behavioral PET studies. It contributes immensely to the possibilities to characterize and unveil the effects and mechanisms of DBS offering valuable clues for future improvements of this therapy.