Mechanism of Action of Deep Brain Stimulation

深部脑刺激的作用机制

• 批准号: 7882393
• 负责人: Kendall H. Lee
• 金额: $ 16.88万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7882393
• 关键词: Action Potentials; Address; Adverse effects; Anatomy; Animal Model; Astrocytes; Basal Ganglia; Basic Science; Behavior; Biomedical Engineering; Brain; Brain imaging; Catecholamines; Cells; Characteristics; Chemistry; Clinic; Clinical; Collaborations; Corpus striatum structure; Deep Brain Stimulation; Dendrites; Development; Devices; Diagnosis; Doctor of Medicine; Doctor of Philosophy; Dopamine; Electric Stimulation; Electrochemistry; Electrodes; Electrophysiology (science); Excitatory Amino Acids; Feedback; Globus Pallidus; Glutamates; Human; Image; Imaging Techniques; In Vitro; Intervention; Lead; Lesion; Life; Location; Measurement; Measures; Mediating; Medical; Mentors; Mentorship; Methods; Microscopic; Modeling; Nerve Endings; Neurologist; Neurology; Neurons; Neurosciences; Neurosurgeon; Neurotransmitters; Operating Rooms; Operative Surgical Procedures; Oxidopamine; Parkinson Disease; Parkinsonian Disorders; Pathway interactions; Pattern; Physiology; Procedures; Program Development; Rattus; Regulation; Research; Research Personnel; Scanning; Signal Transduction; Site; Slice; Structure of subthalamic nucleus; Substantia nigra structure; System; Techniques; Testing; Therapeutic; Therapeutic Effect; Time; Training Programs; Work; career; career development; effective therapy; implantation; in vivo; millisecond; multidisciplinary; neurochemistry; neuronal cell body; neurophysiology; neurosurgery; neurotransmission; neurotransmitter release; next generation; pars compacta; pedunculopontine tegmentum; programs; research study; success; therapeutic effectiveness; time interval

DESCRIPTION (provided by applicant): This proposal describes a 5 year training program for the development of an academic career in neurosurgery. This program will promote the command of electrophysiology, electrochemistry, brain imaging and stereotactic and functional neurosurgery. Dr. Gary Sieck, Chair of Physiology and Biomedical Engineering, will serve as the primary mentor. A mentorship team of experts in brain imaging, electroanalytical chemistry, neuroengineering and neurosurgery will help the applicant elucidate the mechanisms by which Deep Brain Stimulation (DBS) treats Parkinson's disease. Our recent work demonstrates that subthalamic nucleus (STN) DBS may activate nerve endings to release neurotransmitters, including dopamine. The proposed experiments will entail electrophysiologic, electrochemical, and fluorescent microscopic recordings during DBS. The specific aims include the demonstration of 1) DBS results in changes in neuronal action potential firing and release of dopamine in the striatum. 2) The therapeutic benefit of STN DBS is mediated by dopamine release in the 6-OH DA lesioned rat model of Parkinson's disease. 3) STN DBS results in release of glutamate in the STN via astrocytic vesicular release mechanism. This study will be the first detailed analysis of the mechanism of DBS as it relates to DBS effect on astrocytic glutamate release and striatal dopamine release. Success in this project will open a new era in medical diagnosis and intervention, providing precise targeting of DBS electrodes and regulation of neurotransmitter that are critically involved in the therapeutic effectiveness of DBS. The applicant, Kendall Lee, M.D., Ph.D., is a new investigator and a neurosurgeon at the Mayo Clinic Rochester with a multidisciplinary background in neurology, neurosurgery, and neuroscience. He has demonstrated the ability to form unique and effective collaborations. To maximize the likelihood of success, the applicant has enlisted as advisors a highly skilled team of researchers: Charles Blaha, Ph.D. (expert in amperometry), Paul Garris, Ph.D. (expert in Parkinson's disease animal models and fast scan cyclic voltammetry), Eric Newman, Ph.D. (expert in astrocyte research), and Demetrius Maragonore, M.D. (Parkinson's disease Neurologist and researcher). In addition, Fredric Meyer, M.D. (Chair, Neurosurgery Mayo Clinic Rochester) will serve as career development advisor, to make certain a successful career in academic neurosurgery for the applicant.

描述（由申请人提供）：该提案描述了一项为期5年的神经外科学术职业的培训计划。该程序将促进电生理学，电化学，脑成像以及立体定向和功能性神经外科手术的指挥。生理学和生物医学工程主席Gary Sieck博士将担任主要导师。由大脑成像，电分析化学，神经工程和神经外科专家组成的指导团队将有助于申请人阐明深脑刺激（DBS）治疗帕金森氏病的机制。我们最近的工作表明，丘脑下核（STN）DBS可能会激活神经端以释放包括多巴胺在内的神经递质。提出的实验将需要DBS期间的电生理，电化学和荧光微观记录。具体目的包括1）DBS的演示导致神经元动作电势触发和多巴胺在纹状体中的释放发生变化。 2）STN DBS的治疗益处是在帕金森氏病的6-OH DA病变大鼠模型中介导的。 3）STN DBS通过星形细胞囊泡释放机制在STN中释放谷氨酸。这项研究将是对DBS机制的首次详细分析，因为它与DBS对星形胶质细胞释放和纹状体多巴胺释放有关。该项目的成功将在医学诊断和干预方面开放一个新时代，提供DBS电极的精确靶向以及神经递质的调节，这些剂量与DBS的治疗有效性非常重要。申请人肯德尔·李（Kendall Lee），医学博士，博士学位，是梅奥诊所罗切斯特（Mayo Clinic Rochester）的新研究者和神经外科医生，具有神经病学，神经外科和神经科学的多学科背景。他已经证明了建立独特有效合作的能力。为了最大程度地提高成功的可能性，申请人曾担任顾问一支高技能的研究人员团队：Charles Blaha博士。 （安培计量学专家），保罗·加里斯（Paul Garris）博士（帕金森氏病动物模型和快速扫描循环伏击法的专家），埃里克·纽曼（Eric Newman），博士。 （星形胶质细胞研究专家）和医学博士Demetrius Maragonore（帕金森氏病神经病学家和研究人员）。此外，医学博士弗雷德里克·迈耶（Fredric Meyer）（神经外科梅奥诊所主席）将担任职业发展顾问，以确保确定申请人的学术神经外科事业。