Development of globus pallidus externus stimulation for Parkinson's disease

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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.