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Neuroprotection of Dopamine During Microdialysis

微透析过程中多巴胺的神经保护

基本信息

批准号：
8657494
负责人：
Adrian C Michael
金额：
$ 19.03万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-05-01 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8657494
关键词：
Affect Animal Model Anti-Inflammatory Agents Anti-inflammatory Apoptosis Astrocytes Behavior Biological Assay Blood - brain barrier anatomy Blood flow Brain Brain Chemistry Caspase Cells Central Nervous System Diseases Cicatrix Cytoprotective Agent Devices Dexamethasone Dialysis procedure Disease Dopamine Electrons Endothelium Extracellular Space Figs - dietary Fluorescence Microscopy Glial Fibrillary Acidic Protein Gliosis Goals Human Implant Injury Internet Investigation Ischemia Laboratories Life Liquid substance Measurement Measures Membrane Microdialysis Microglia Molecular Molecular Weight Monitor Neurons Neuroprotective Agents Neurosciences Neurotransmitters Normal tissue morphology Outcome Outcomes Research Oxidants Pathology Patients Penetration Pharmaceutical Preparations Physiological Public Health Publications Research Research Personnel Role Sampling Science Site Techniques Tissues Tyrosine 3-Monooxygenase Yang brain tissue clinical care deep brain stimulator dopamine transporter drug discovery extracellular flexibility fluoro jade implantation improved injured neurochemistry neuroprosthesis neuroprotection nitroxyl novel public health relevance research study response sensor small molecule tool

项目摘要

DESCRIPTION (provided by applicant): Microdialysis is widely used in animal models and human patients to monitor and assess the extracellular neurochemistry of the living, intact brain. It has made significant contributions to the study of the neurochemistry of behavior, CNS pathology, drug discovery, and clinical care. Despite its many beneficial attributes, microdialysis suffers from an overlooked drawback in that implanting the probes causes a penetration injury to the tissues being analyzed. The penetration injury results in opening of the blood brain barrier, ischemia of the tissue surrounding the probe, and the activation of astrocytes that eventually engulf the probe track in a glial scar. The penetration injury affects the outcome of microdialysis experiments, i.e. the results reflect the neurochemical attributes of the injured, rather than normal, tissues. The goal of the research proposed here is to establish the feasibility of ameliorating the penetration injury and its impact on microdialysis results by the combined use of a powerful anti-inflammatory drug, dexamethasone, and a novel mitochondrially-targeted electron and radical scavenging cytoprotective agent. The outcome of this research will have a lasting and significant impact on the several branches of neuroscience that involve the insertion of devices into brain tissues, including microdialysis, electrochemical sensors, and neuroprosthetic devices such as deep brain stimulators and neuron recordings arrays.

描述（由申请人提供）：微透析广泛用于动物模型和人类患者，以监测和评估活体完整大脑的细胞外神经化学。它对行为神经化学、中枢神经系统病理学、药物发现和临床护理的研究做出了重大贡献。尽管微透析有许多有益的特性，其存在一个被忽视的缺点，即植入探针会对被分析的组织造成穿透损伤。穿透损伤导致血脑屏障打开、探针周围组织缺血以及星形胶质细胞激活，最终将探针轨迹吞没在神经胶质疤痕中。渗透损伤影响微透析实验的结果，即结果反映了受伤组织而不是正常组织的神经化学属性。这里提出的研究的目标是确定可行性通过联合使用强效抗炎药地塞米松和新型线粒体靶向电子和自由基清除细胞保护剂，改善渗透损伤及其对微透析结果的影响。这项研究的结果将对神经科学的几个分支产生持久和重大的影响，这些分支涉及将设备插入脑组织，包括微透析、电化学传感器和神经假体设备，例如深部脑刺激器和神经元记录阵列。