高频电刺激丘脑底核对偏侧帕金森病猴模型苍白球内侧部神经元放电的影响

Effect of high frequency stimulation of subthalamic nucleus on discharge changes of globus pallidus nucleus in primate models of Parkinson＂ s disease

目的探讨深部电刺激丘脑底核（STN）治疗帕金森病fPD）的可能作用机制。方法通过在模型猴单侧大脑注入1．甲基．4-苯基-1，2，3，6-四氢吡啶（MPTP）制备偏侧PD模型，随后在立体定向技术下参照猴脑立体定向图谱，将记录的玻璃微电极和刺激电极分别插入苍白球内侧部（Gpi）和STN内，通过单细胞胞外记录法记录并分析神经元刺激前和刺激时的放电改变情况。结果PD猴未注药侧GPi神经元自发放电较规则，放电频率为（44．38±13．66）锋电位／s；注药侧GPi神经元放电频率为（50．57±15．53）锋电位／s，较未注药侧稍快但差异无统计学意3Z（P〉0．05）。刺激过程中GPi神经元存在4种反应：部分抑制、完全抑制、兴奋和无变化，多数神经元表现为受到抑制，注药侧更为明显，平均抑制率为56．29％±29．66％，高于未注药侧的36．03％±35．25％．差异有统计学意义（P〈0．05）。结论深部电刺激术治疗PD的作用机制为通过高频刺激对STN神经元异常兴奋性的调控，改变相关的联系核团如GPi或黑质网状部（SNr）异常功能状态，最终使基底节运动环路正常控制功能重新恢复，进而改善PD症状。

Objective To investigate the mechanism of high frequency stimulation （HFS） of subthalamic nucleus （STN） in treating primate models of Parkinson＇s disease （PD）. Methods Two rhesus monkeys were injected 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine （MPTP） into unilateral brain to induce the PD models; rhesus monkey models were implanted with glass recording electrodes and stimulating electrodes into the globus pallidus internus （GPi） and STN, respectively. Extracellular recording was used to investigate the spikes and analyze the firing activity of GPi before and during STN-HFS. Results The spontaneous firing of GPi neurons on the normal side of PD monkeys was more regular than that on the abnormal side, and the frequency of firing was （44.38±13.66）spike/s and （50.57±15.53）spike/s respectively, without significant difference （P〉0.05）. During STN-HFS, 4 neuronal activity changes existed, including incomplete inhibition, complete inhibition, increase of excitability and no change. STN-HFS could cause inhibition in most of the GPi neurons on both sides and the average inhibition rate on the abnormal side was 56.29%±29.66%, which was higher than that on the normal side（36.03%±35.25%）,with statistically significant difference（P〈0.05）. Conclusion HFS would do a certain extent suppression to the abnormal activity of STN neurons, resulting in a requilibrium in the neuronal activity of the basal ganglia motor circuit and the improvement of PD symptoms.