Deep brain stimulation of the subthalamic nucleus treats Parkinson's disease through enhancing metabolic activity of the corpus striatum Verification by single photon emission computed tomography and positron emission tomography

摘要

BACKGROUND:Subthalamic nucleus deep brain stimulation (STN DBS) for Parkinson's disease (PD) has achieved good effects,but to date the mechanism of STN DBS remains poorly understood. STN DBS may increase dopamine levels or metabolic activity of the corpus striatum. OBJECTIVE:To validate the effects of STN DBS on dopamine metabolism and glucose metabolism in the corpus striatum of hemiparkinsonian monkeys using single photon emission computed tomography (SPECT) and position emission tomography (PET). DESIGN,TIME AND SETTING:A controlled animal study was performed at the Neurosurgery Laboratory,Changhai Hospital of the Second Military Medical University of Chinese PLA between January 2004 and December 2007. METHODS:Hemiparkinsonism was induced in adult Rhesus Macaque monkeys,which exhibit similar characteristics of PD in humans,through unilateral internal carotid artery infusion of 1-methy-4-phenyl-1,2,3,6-tetrahydropyrindine. Following model establishment,stimulation electrodes were implanted in the right STN,and chronic high-frequency stimulation (60 μs pulse width,130 Hz frequency,and 1.5-2.0 V pressure) was performed. MAIN OUTCOME MEASURES:The changes in dopamine transporter (DAT),D2 receptor (D2R),and glucose metabolism in the corpus striatum following STN DBS were observed using SPECT and PET. RESULTS:SPECT examination showed that DAT specific binding in the right corpus striatum was increased at 3 months after DBS compared with prior to stimulation,and D2R specific binding in the right corpus striatum gradually decreased near levels on the left (non-electrode-implanted) side within 3 months after DBS. PET examination showed that the glucose metabolism in the right corpus striatum was markedly increased at 3 months after effective DBS. Hemiparkinsonism monkeys showed improved left limb rigidity,increased activities,and stable gait under chronic high-frequency stimulation. CONCLUSION:STN DBS increased striatal DAT,decreased D2R,and enhanced glucose metabolism,suggesting that chronic,high-frequency STN stimulation enhanced the metabolic activity of the corpus striatum,a mechanism for improving the PD symptoms of hemiparkinsonian monkeys.