摘要
深脑核团电刺激(DBS)已成为改善帕金森病人运动障碍的有效治疗手段,然而其确切的治疗机制仍然不明。目前,DBS机制探究系统多由电刺激仪器和信号检测仪器两部分构成,多台实验设备的长期开启易产生操作程序复杂、环境噪声增多和资源浪费等问题。本研究建立了一套综合性实验系统,包括将电刺激功能与神经双模信号检测功能集成的神经电调控-双模信号检测仪器和基于微机电加工技术制备的微电极阵列(MEA)。在体实验前,对经纳米铂黑和Nafion膜修饰的MEA进行体外标定。实验结果表明,1~50μmol/L多巴胺(DA)溶液与修饰后的电极表面氧化电流值呈良好的线性关系,线性相关系数为0.998。随后,设计并进行了以前脑内侧束为电刺激靶点,纹状体为神经信息检测核团的活体大鼠实验。实验结果表明,纹状体内DA浓度在刺激后迅速上升,最高达2.06μmol/L,约为刺激前水平的1.57倍;神经元动作电位发放率增加,由刺激前的1.17 Hz上升至6.77 Hz;场电位活动增强,功率由刺激前的0.19 mW上升至0.64 mW。本研究设计并制备的神经电调控-双模信号检测系统实现了电刺激与双模信号检测的功能集成,有望为DBS治疗机制的探究提供有效实验工具。
Although deep brain stimulation(DBS)has become an effective treatment for improving dyskinesia in Parkinson’s disease,the exact treatment mechanism remains unclear.In addition,the current system researching DBS mechanism is always composed of two individual parts:the electrical stimulation instrument and the signal detection instrument,which makes it easy to cause the complicated operation of procedure and the waste of resource.In this work,a comprehensive experimental system was established,including an electrostimulation-detection instrument which integrated the function of electrical stimulation and neural signal detection,and the microelectrode arrays(MEA)which were fabricated by micro-electro-mechanical system(MEMS)and modified by nanoplatinum and nafion membrane.Experimental results showed that dopamine in concentration range of 1-50μmol/L had a good linear relationship with the surface oxidation current of the modified MEA,and the linear correlation coefficient was 0.998.What’s more,DBS was designed with the medial forebrain bundle(MFB)as stimulation target and the striatum as detection area,which made the striatal simultaneous observation of dopamine concentration and neuronal firing was achieved while electrical stimulation was applied.Experimental results indicated that the concentration of dopamine in the striatum increased rapidly after stimulation,reaching a maximum of 2.06μmol/L which was about 1.57 times of the pre-stimulation level;the spike firing rate increased from 1.17 Hz to 6.77 Hz;and the power of local field potential was enhanced from 0.19 mW to 0.64 mW.The electrostimulation-detection system developed in this study realized the integration of electrical stimulation and dual-mode signal detection,which simplified the complex experimental steps and was expected to provide an effective experimental tool for the exploration of DBS treatment mechanism.
作者
张禹
徐声伟
何恩慧
肖桂花
宋轶琳
高飞
王蜜霞
蔡新霞
ZHANG Yu;XU Sheng-Wei;HE En-Hui;XIAO Gui-Hua;SONG Yi-Lin;GAO Fei;WANG Mi-Xia;CAI Xin-Xia(State Key Laboratory of Transducer Technology,Institute of Electronics,Chinese Academy of Sciences,Beijing 100190,China;University of Chinese Academy of Sciences,Beijing 100049,China)
出处
《分析化学》
SCIE
EI
CAS
CSCD
北大核心
2019年第10期1703-1709,共7页
Chinese Journal of Analytical Chemistry
基金
国家纳米科技重点研发计划(No.2017YFA0205902)
国家自然科学基金项目(Nos.61527815,61601435,61775216,61771452)
中国科学院前沿科学重点研究项目(No.QYZDJ-SSW-SYS015)资助~~
关键词
深脑核团电刺激
微电极阵列
多巴胺
神经电生理信号
神经递质
Deep brain stimulation
Microelectrode arrays
Dopamine
Neuro-electrophysiological signal
Neurotransmitters