恒河猴腦深部電刺激雙側伏隔核模型建立的研究
發(fā)布時間：2018-09-09 17:57
【摘要】： 背景及目的: 非人靈長類動物恒河猴是研究腦功能的重要實驗動物,也是研究腦深部電刺激(deep brain stimulation, DBS)機理及應用的理想動物模型。DBS的作用與其電極所在位置密切相關,其治療效果依賴于相應靶點的準確定位。因此,在利用恒河猴進行DBS相關研究時,其深部核團的準確定位非常重要。然而,現(xiàn)有實驗中恒河猴腦深部核團的定位主要是根據(jù)猴腦立體定向圖譜中的坐標值確定。這種方法的缺陷性是顯而易見的,由于猴的不同種系、個體的差別,相同腦核團的坐標值必然有差異;甚至不同猴腦圖譜間相同核團的坐標值也不相同,這與圖譜采用不同標本有關。臨床上的立體定向技術早已實現(xiàn)了影像學輔助靶點定位,同時有專用的儀器設備用于DBS植入。然而,由于恒河猴的頭顱遠小于人類,臨床上所用有框架立體定向手術系統(tǒng)無法直接用于實驗動物。因此,我們設計并制作了立定定向頭環(huán)適配器,該適配器大小介入恒河猴頭顱和頭環(huán)之間,可固定于猴頭顱上,并與頭環(huán)緊密結合。該適配器的引入相當于擴大了恒河猴的頭圍,使MRI引導有框架立體定向手術系統(tǒng)用于恒河猴成為可能。本研究以伏隔核作為腦深部核團的代表,對采用上述方法準確、個性化定位恒河猴腦深部核團及DBS電極的植入模型建立進行了探討。 方法 第一階段,以2只恒河猴頭顱通過自制適配器固定于CRW-FN立體定位頭架,行1.0T磁共振薄層掃描,參考恒河猴腦磁共振和病理對照圖譜確定雙側伏隔核位置并計算其坐標,行雙側伏隔核射頻毀損術,術后1周,行3.0T磁共振薄層掃描,觀察毀損灶位置,測量與同側伏隔核預定靶點的距離。第二階段,以4只恒河猴頭顱通過自制適配器固定于CRW-FN立體定位頭架,行1.0T磁共振薄層掃描,參考恒河猴腦磁共振和病理對照圖譜確定雙側伏隔核位置并計算其坐標,植入腦深部電刺激(deep brain stimulation, DBS)電極,利用耳腦膠及內固定鈦網(wǎng)固定電極于骨窗處,余部分置于項背部皮下;術后1周,行1.0T磁共振薄層掃描,觀察電極位置,測量8個DBS電極末端與同側伏隔核預定靶點的距離。并進行電刺激檢驗。 結果 設計出準確的可調節(jié)恒河猴腦深部核團定位方法,使2只恒河猴成功準確毀損雙側伏隔核,術后磁共振復查毀損灶前后方向上差距為0.65±0.35mm,左右方向上差距為0.43±0.17mm。使4只恒河猴均成功植入雙側電極,術后磁共振復查示電極顱內部分無彎曲、移位,電極末端與伏隔核中心前后方向差距為0.64±0.28mm,左右方向差距為0.34±0.17mm。電刺激檢驗有效植入。 結論 通過自制適配器,可以將臨床MRI引導有框架立體定向手術系統(tǒng)用于恒河猴,實現(xiàn)個性化、準確的腦深部核團定位并可適用于其他非人靈長類。成功建立恒河猴腦深部電刺激伏隔核模型。
[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 鹵0.35mm and 0.43 鹵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 鹵0.28 mm and 0.34 鹵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.
【學位授予單位】：第四軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2010
【分類號】：R-332
本文編號：2233142
[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 鹵0.35mm and 0.43 鹵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 鹵0.28 mm and 0.34 鹵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.
【學位授予單位】：第四軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2010
【分類號】：R-332
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