Chronic deep brain stimulation of the subthalamic nucleus in a monkey model of hemiparkinsonian Dynamic alterations of extracellular fluid dopamine levels in corpus striatum

摘要

BACKGROUND: Although experimental studies have utilized high-frequency stimulation in animalmodels, few reports have focused on long-term subthalamic nucleus deep brain stimulation (STNDBS)in Parkinson's disease (PD) animal models.OBJECTIVE: The present study simulated long-term DBS system and utilized microdialysistechnology to study the influence of STN DBS on levels of extracellular dopamine (DA) and itsmetabolites, homovanillic acid (HVA) and dihydroxy phenyl acetic acid, in the corpus striatum of ahemiparkinsonian monkey model.DESIGN, TIME AND SETTING: A controlled animal study was performed at the NeurosurgeryLaboratory, Changhai Hospital of the Second Military Medical University of Chinese PLA betweenJanuary 2004 and December 2007.MATERIALS: 1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyrindinewas (MPTP) purchased from Sigma,USA. Type-3389 DBS electrode and type-7246 pulse generator were provided by Medtronic, USA.METHODS: Hemiparkinsonism was induced in 2 male, adult Rhesus Macaque monkeys throughunilateral internal carotid artery infusion of MPTP. Following model establishment, stimulationelectrodes were implanted in the right STN, and chronic high-frequency stimulation (60 μs pulsewidth, 130 Hz frequency, and 1.5 2.0 V pressure) was performed.MAIN OUTCOME MEASURES: Prior to, and 2 hours, 8 hours, 1 week, 1 month, and 2 months afterDBS, samples were collected from the caudate nucleus and putamen using microdialysis technologyExtracellular levels of DA and its metabolites were measured using high-performance liquidchromatography and electrochemical detection (HPLC-ECD) methods.RESULTS: At 8 hours, 1 week, 1 month, and 2 months after DBS, DA levels in the putamen andcaudate nucleus were increased on the electrode-implanted side by 39%, 91%, 111%, and 114%and 31%, 91%, 106%, and 102%, respectively. The DA turnover rate (HVA/DA) was increased in theputamen and caudate nucleus by 186% and 91%, respectively, at 8 hours after DBS, while therewas no significant difference at 1 week, 1 month, and 2 months after DBS.CONCLUSION: Effective, chronic, high frequency DBS increased extracellular DA levels in thecorpus striatum, which could be one of mechanisms involved in the effects of STN DBS.