Dockx Robrecht, Peremans Kathelijne, Vlerick Lise, Van Laeken Nick, Saunders Jimmy H, Polis Ingeborgh, De Vos Filip, Baeken Chris
Ghent Experimental Psychiatry (GHEP) lab, Department of Psychiatry and Medical Psychology, Ghent University, Ghent, East Flanders, Belgium.
Department of Veterinary medical imaging and small animal orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, East Flanders, Belgium.
PLoS One. 2017 Sep 22;12(9):e0185362. doi: 10.1371/journal.pone.0185362. eCollection 2017.
Currently, the rat has been a useful animal model in brain stimulation research. Nevertheless, extrapolating results from rodent repetitive Transcranial Magnetic Stimulation (rTMS) research to humans contains several hurdles. This suggests the desperate need for a large animal model in translational rTMS research. The dog would be a valid choice, not only due to the fact that humans and dogs share a neurophysiological background, but a similar neuropathological background as well.
In order to evaluate the feasibility of the canine rTMS animal model, this study aimed to evaluate the neurophysiological response in dogs on a, clinically used, accelerated high frequency (aHF) rTMS protocol. This aHF-rTMS (20 Hz) protocol was performed under anaesthesia or sedation and either 20 sessions or 5 sessions were given to each dog.
21 healthy dogs were randomly subjected to one of the four aHF-rTMS protocols (1 sham and 3 active protocols). For each dog, the perfusion indices (PI), of a [99mTc]HMPAO scan at 4 time points, for the left frontal cortex (stimulation target) were calculated for each protocol.
Concerning sham stimulation, the average PI remained at the baseline level. The main result was the presence of a direct transitory increase in rCBF at the stimulation site, both under anaesthesia and sedation. Nevertheless the measured increase in rCBF was higher but shorter duration under sedation. The magnitude of this increase was not influenced by number of sessions. No changes in rCBF were found in remote brain regions.
This study shows that, despite the influence of anaesthesia and sedation, comparable and clinically relevant effects on the rCBF can be obtained in dogs. Since less methodological hurdles have to be overcome and comparable results can be obtained, it would be acceptable to put the dog forward as an alternative translational rTMS animal model.
目前，大鼠已成为脑刺激研究中一种有用的动物模型。然而，将啮齿动物重复经颅磁刺激（rTMS）研究的结果外推至人类存在若干障碍。这表明在转化性rTMS研究中迫切需要一种大型动物模型。狗将是一个有效的选择，这不仅是因为人类和狗具有相似的神经生理背景，还具有相似的神经病理背景。
为了评估犬rTMS动物模型的可行性，本研究旨在评估犬在临床使用的加速高频（aHF）rTMS方案下的神经生理反应。该aHF-rTMS（20Hz）方案在麻醉或镇静状态下进行，每只狗接受20次或5次刺激。
21只健康犬被随机分配至四种aHF-rTMS方案之一（1种假刺激和3种有效方案）。对于每只狗，计算每种方案在4个时间点对左侧额叶皮质（刺激靶点）进行[99mTc]HMPAO扫描的灌注指数（PI）。
关于假刺激，平均PI保持在基线水平。主要结果是，在麻醉和镇静状态下，刺激部位的局部脑血流量（rCBF）均出现直接短暂增加。然而，镇静状态下测得的rCBF增加幅度更高，但持续时间更短。这种增加的幅度不受刺激次数的影响。在远处脑区未发现rCBF有变化。
本研究表明，尽管存在麻醉和镇静的影响，但在犬中可获得对rCBF的可比且具有临床相关性的效应。由于需要克服的方法学障碍较少且可获得可比结果，因此将狗作为一种替代性的转化性rTMS动物模型是可以接受的。
