恒河猴脑深部电刺激双侧伏隔核模型建立的研究

发布时间：2018-09-09 17:57

【摘要】： 背景及目的: 非人灵长类动物恒河猴是研究脑功能的重要实验动物,也是研究脑深部电刺激(deep brain stimulation, DBS)机理及应用的理想动物模型。DBS的作用与其电极所在位置密切相关,其治疗效果依赖于相应靶点的准确定位。因此,在利用恒河猴进行DBS相关研究时,其深部核团的准确定位非常重要。然而,现有实验中恒河猴脑深部核团的定位主要是根据猴脑立体定向图谱中的坐标值确定。这种方法的缺陷性是显而易见的,由于猴的不同种系、个体的差别,相同脑核团的坐标值必然有差异;甚至不同猴脑图谱间相同核团的坐标值也不相同,这与图谱采用不同标本有关。临床上的立体定向技术早已实现了影像学辅助靶点定位,同时有专用的仪器设备用于DBS植入。然而,由于恒河猴的头颅远小于人类,临床上所用有框架立体定向手术系统无法直接用于实验动物。因此,我们设计并制作了立定定向头环适配器,该适配器大小介入恒河猴头颅和头环之间,可固定于猴头颅上,并与头环紧密结合。该适配器的引入相当于扩大了恒河猴的头围,使MRI引导有框架立体定向手术系统用于恒河猴成为可能。本研究以伏隔核作为脑深部核团的代表,对采用上述方法准确、个性化定位恒河猴脑深部核团及DBS电极的植入模型建立进行了探讨。方法第一阶段,以2只恒河猴头颅通过自制适配器固定于CRW-FN立体定位头架,行1.0T磁共振薄层扫描,参考恒河猴脑磁共振和病理对照图谱确定双侧伏隔核位置并计算其坐标,行双侧伏隔核射频毁损术,术后1周,行3.0T磁共振薄层扫描,观察毁损灶位置,测量与同侧伏隔核预定靶点的距离。第二阶段,以4只恒河猴头颅通过自制适配器固定于CRW-FN立体定位头架,行1.0T磁共振薄层扫描,参考恒河猴脑磁共振和病理对照图谱确定双侧伏隔核位置并计算其坐标,植入脑深部电刺激(deep brain stimulation, DBS)电极,利用耳脑胶及内固定钛网固定电极于骨窗处,余部分置于项背部皮下;术后1周,行1.0T磁共振薄层扫描,观察电极位置,测量8个DBS电极末端与同侧伏隔核预定靶点的距离。并进行电刺激检验。结果设计出准确的可调节恒河猴脑深部核团定位方法,使2只恒河猴成功准确毁损双侧伏隔核,术后磁共振复查毁损灶前后方向上差距为0.65±0.35mm,左右方向上差距为0.43±0.17mm。使4只恒河猴均成功植入双侧电极,术后磁共振复查示电极颅内部分无弯曲、移位,电极末端与伏隔核中心前后方向差距为0.64±0.28mm,左右方向差距为0.34±0.17mm。电刺激检验有效植入。结论通过自制适配器,可以将临床MRI引导有框架立体定向手术系统用于恒河猴,实现个性化、准确的脑深部核团定位并可适用于其他非人灵长类。成功建立恒河猴脑深部电刺激伏隔核模型。
[Abstract]:Background and objective: rhesus monkey, a non-human primate, is an important laboratory animal for the study of brain function. It is also an ideal animal model for studying the mechanism and application of deep brain electrical stimulation (deep brain stimulation, DBS). The role of DBS is closely related to the location of its electrode, and its therapeutic effect depends on the accurate location of the corresponding target. Therefore, it is very important to accurately locate the deep nuclei of rhesus monkeys in DBS correlation research. However, the localization of the deep nuclei of the Ganges monkey brain is mainly determined by the coordinate values in the stereotactic map of the monkey brain. The defect of this method is obvious. Because of the different species and individuals of monkeys, the coordinate values of the same brain nuclei must be different, and even the coordinate values of the same nuclei are different among different monkey brain maps. This is related to the use of different specimens in the atlas. The clinical stereotactic technique has already realized radiographically assisted target location and has a special instrument for DBS implantation. However, because the head of rhesus monkey is much smaller than that of human, the frame stereotactic surgery system used in clinic can not be used directly in laboratory animals. Therefore, we have designed and manufactured a vertical directional head ring adapter, which can be attached to the head of a rhesus monkey and can be tightly combined with the head ring of a rhesus monkey by the size of the adapter. The introduction of the adapter is equivalent to enlarging the rhesus monkey's head circumference, making it possible to use the MRI guided stereotactic surgery system in rhesus monkeys. In this study, the nucleus accumbens was used as the representative of the deep nucleus of the brain, and the establishment of the implanted model of the deep nucleus and DBS electrode of monkey by using the above method was discussed. Methods in the first stage, the heads of two rhesus monkeys were fixed on the CRW-FN stereotactic head frame by self-made adapters. The location of bilateral nucleus accumbens was determined and its coordinates were calculated by referring to the magnetic resonance and pathological maps of Ganges monkey brain. Radiofrequency ablation of bilateral nucleus accumbens was performed. 1 week after operation, thin-layer magnetic resonance scanning was performed at 3.0T to observe the location of the lesion. The distance from the predetermined target of the ipsilateral nucleus accumbens was measured. In the second stage, the head of four rhesus monkeys were fixed on the CRW-FN stereotactic head frame by self-made adapters, and were scanned with 1.0T Mr thin layer. The location of bilateral nucleus accumbens was determined and its coordinates were calculated by referring to the magnetic resonance imaging and pathological comparative atlas of the monkey brain. The (deep brain stimulation, DBS) electrode was implanted into the deep brain to stimulate the brain, and the osseous window was fixed with otorencephalic glue and titanium mesh fixation electrode, the rest was placed subcutaneously on the back of the nape, 1 week after operation, 1.0T thin layer magnetic resonance imaging was performed to observe the position of the electrode. The distance between the ends of 8 DBS electrodes and the predetermined targets of ipsilateral nucleus accumbens was measured. Electric stimulation test was performed. Results an accurate and adjustable method was designed to locate the deep nuclei in the brain of rhesus monkey, and 2 rhesus monkeys were successfully destroyed the bilateral nucleus accumbens. The difference before and after the lesion was 0.65 卤0.35mm and 0.43 卤0.17mm. Four rhesus monkeys were successfully implanted with bilateral electrodes. After operation, MRI examination showed that the intracranial part of the electrode was not bent and shifted. The distance between the end of the electrode and the center of nucleus accumbens was 0.64 卤0.28 mm and 0.34 卤0.17 mm respectively. Electrical stimulation test was effective. Conclusion the clinical MRI guided stereotactic surgery system can be used in rhesus monkeys by self-made adaptor to realize individualized and accurate localization of deep brain nuclei and can be applied to other non-human primates. The model of deep brain stimulation of nucleus accumbens was established successfully.
【学位授予单位】：第四军医大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R-332

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