Development of globus pallidus externus stimulation for Parkinson's disease

为了建立帕金森病(PD)的灵长类动物模型，我们给食蟹猴注射了1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)。帕金森症状的定量评估采用Gash的帕金森病偏侧灵长类动物评定量表(Gash‘s Scale)。照顾这些动物是按照熊本大学动物资源与开发中心颁布的规定进行的。在全身麻醉下，动物接受间歇性注射MPTP(1.2 mg/kg)，持续数周。4-8周后，动物出现帕金森综合症，Gash‘s评分超过15分。然后通过立体定向手术将四极脑深部刺激电极植入苍白球。用S参数(130~160 Hz，90μ)电刺激苍白球内脑部，可明显改善帕金森病的体征。电刺激苍白外球(参数：5 Hz，90~100μ，S)可使帕金森症状减轻6~7分。对这两只动物的尸检显示，黑质中的多巴胺能神经元明显枯竭，电极已插入苍白球。

In order to produce the primate model of Parkinson's disease (PD), we injected 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to Cynomolgus monkeys. For quantitative assessment of parkinsonian symptoms, the Gash's hemi-parkinsonian primate rating scale (Gash's scale) was used. Care of the animals was in accordance with regulations promulgated by the Center for Animal Resources and Development of Kumamoto University. Under general anesthesia, animals received an intermittent administration of MPTP (1.2 mg/kg) per each for several weeks. After 4-8 weeks, the animals developed parkinsonism showing more than 15 points with Gash's scale. Quadripolar deep brain stimulation (DBS) electrodes were then implanted into the globus pallidus using the stereotactic surgical procedures. Electrostimulation of the globus pallidus internus with the parameters (130-160Hz and 90μs) produced significant improvement of parkinsonian signs, as shown in treatment of patients with PD.Stimulation of the globus pallidus externus with the parameters (5Hz and 90-100μs) also alleviated the parkinsonism by reducing 6-7 points of Gash's scale. Postmorten examinations on the two animals showed that there was marked depletion of dopaminergic neurons in the substantia nigra and that the electrodes had been inserted into the globus pallidus.