偏侧猴PD模型STN慢性高频电刺激对脑内多巴胺系统的影响

目的探讨丘脑底核(STN)慢性高频电刺激对猴偏侧帕金森病(PD)模型脑内多巴胺(DA)系统的影响。方法采用单侧颈内动脉注入1-甲基-4-苯基-1,2,3,6四氢吡啶(MPTP)建立猴偏侧PD模型2只,体内植入脑深部电刺激(DBS)系统,行右侧STN慢性高频电刺激。在电刺激前后不同时间点采用微透析技术检测纹状体区细胞外液的多巴胺(DA)及其代谢产物高香草酸(HVA)含量,腰穿取脑脊液标本测量脑脊液中DA、HVA含量,单光子放射计算机断层扫描(SPECT)检测脑内纹状体区巴胺转运体(DAT)及多巴胺D2受体(D2R)的变化。结果猴偏侧PD模型在给予单侧STN慢性高频电刺激后纹状体区DA、HVA明显增高。SPECT显示在有效刺激后纹状体区DAT特异性摄取率增高,D2R特异性摄取率下降。脑脊液中多巴胺及其代谢产物的含量与术前相比无明显差异。结论通过微透析检测提示在给予STN有效慢性高频电刺激后提高了纹状体区DA及其代谢产物的升高,DAT特异性摄取率增高,D2R特异性摄取率下降提示纹状体区的代谢活性有明显升高,这可能是STN-DBS治疗帕金森病的重要机制之一。

Influence of dopamine system in hemiparkinsonism monkey model with high frequency stimulation of subthalamic nucleus

Objective To investigate influence of dopamine(DA) system in hemiparkinsonism monkey model with high frequency stimulation of subthalamic nucleus(STN).Methods Two hemiparkinsonian monkeys induced by right internal carotid artery infusion of 1-methy-4-phenyl-1,2,3,6-tetrahydropy-rindine(MPTP) were implanted deep brain stimulation(DBS) system and underwent right STN chronic high frequency stimulation.Dopamine(DA) and its metabolites homovanillic acid(HVA) in striatum and cerebrospinal fluid(CSF) were detected before and after high frequency stimulation.SPECT examination were performed to observe the changes of dopamine transporter(DAT) and D2receptor(D2R) in striatum.Results DA and HVA in right striatum of hemiparkinsonism monkeys increased significantly after high frequency stimulation.SPECT imaging indicated DAT of right striatum increased,and D2R decreased to the level of unlesioned side.DA and HVA in CSF have no difference compared with preoperative.Conclusion The content of DA and its metabolites can be increased obviously by high frequency stimulation of STN.After stimulation,the DAT of striatum increased,and D2R decreased,indicated that DA metabolic activity promoted significantly.So,we think that change of DA system maybe one of important mechanisms of PD treatment by STN-DBS.