Microdialysis Studies of Seizure-Induced Oxidative Stress

癫痫发作引起的氧化应激的微透析研究

基本信息

批准号：
7696861
负责人：
CRAIG E LUNTE
金额：
$ 38.97万
依托单位：
UNIVERSITY OF KANSAS LAWRENCE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-16 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7696861
关键词：
8-hydroxyguanosine Acetic Acids Acetonitriles Acids Acrolein Affect Aldehydes Algorithms Aliquot Alprostadil Amino Acid Neurotransmitters Amino Acids Animals Anions Anterior Arachidonic Acids Area Behavioral Benzoquinones Biochemical Biochemical Pathway Biological Biological Markers Blood capillaries Brain Brain region Budgets Buffers Cannulas Capillary Electrophoresis Carbon Carboxylic Acids Catecholamines Chemicals Chromatography Chronic Circadian Rhythms Clinical Cobalt Complex Control Animal Control Groups Corpus striatum structure Coupled Coupling Cyanides Cysteine DNA DNA Damage Data Detection Development Dinoprost Dinoprostone Disulfides Dose Electrodes Epilepsy Equipment Evaluation Event F2-Isoprostanes Femoral vein Fiber Fluorescence Funding Future Generalized seizures Generations Glutamates Glutathione Glutathione Disulfide Goals High Pressure Liquid Chromatography Hippocampus (Brain)Hour Human Hydrazine Hydrazines Hydrofluoric Acid Hydroquinones Immunoassay Impact Seizures Implant Infusion procedures Injection of therapeutic agent Kindling (Neurology)Knowledge Laboratories Lasers Lateral Lead Lipid Peroxidation Lipids Location London Measures Metabolism Methodology Methods Micellar Electrokinetic Capillary Chromatography Microdialysis Microelectrodes Modeling Modification Monitor Muscle Neurologic Neurons Neurosciences Operative Surgical Procedures Outcome Oxidative Stress Paste substance Pathway interactions Pentylenetetrazole Perfusion Phase Phosphate Buffer Plasma Population Positioning Attribute Procedures Prostaglandin D2 Prostaglandins Proteins Rattus Reactive Oxygen Species Reagent Recovery Relative (related person)Reporting Research Resolution Role Ruthenium Saline Sampling Scheme Seizures Signal Transduction Skin Specificity Spinal Cord Staging Status Epilepticus Students Study Section Sulfhydryl Compounds Surface System Techniques Time TimeLine Tissue Sample Tissues Training Treatment Protocols Urine Wages Water Work adduct analytical method autooxidation base capillary carbon fiber clinically relevant design excitotoxicity ferrocyn functional group gamma-Aminobutyric Acid hydroquinone improved insight instrument interest ionization method development multiple reaction monitoring neurotoxic neurotoxicity neurotransmitter release oxidation oxidative damage phthalocyanine progesterone 11-hemisuccinate-(2-iodohistamine)research study response small molecule

项目摘要

We propose to investigate the role of epileptic seizures in oxidative stress. There is a wealth of research that demonstrates epileptic seizures lead to the formation of reactive oxygen species (ROS), which cause oxidative damage to DNA, lipids, and proteins. We intend to investigate the role of excitotoxic catecholamine release during epileptic seizures and their role in the formation of ROS leading to oxidative stress. We will use microdialysis sampling in discrete brain regions along with simultaneous recording of electrocorticographic (ECoG) activity to probe chemical and electrographic activity changes in the brain associated with seizures. This will allow us to correlate biomarker levels with seizure activity. Microdialysis sampling will be used to continuously monitor several biochemical pathways prior to, during, and after induction of seizures. Microdialysis experiments will provide both temporal and spatial information about oxidative stress caused by seizures and the brains response to them. This dual approach will allow us to resolve questions that have remained unclear using plasma and urine sampling and standard tissue sampling techniques. Methods previously developed in the PI’s laboratory will be used to monitor formation of ROS, biomarkers for DNA damage, and the neurotransmitter amino acids and catecholamines. New analytical methods will be developed to monitor aldehydes produced through lipid peroxidation, endogenous thiols and disulfides involved in protection from ROS, and prostanoids resulting from arachidonic acid metabolism. Initially, we will use a chemically-induced seizure model using 3-mercaptopropionic acid (3-MPA). Coupled to the advanced analytical methodology and microdialysis sampling, we will then investigate the neurological events leading from seizures to oxidative stress. In particular, the temporal relationship between oxidative stress (as measured by ROS formation), and neuroexcitation (as measured by the GABA/glutamate ratio and the catecholamines) will be determined and correlated to the duration and intensity of seizure episodes.

我们建议研究癫痫发作在氧化应激中的作用，大量研究表明癫痫发作会导致活性氧 (ROS) 的形成，从而对 DNA、脂质和蛋白质造成氧化损伤。研究癫痫发作期间兴奋性毒性儿茶酚胺释放的作用及其在导致氧化应激的 ROS 形成中的作用我们将在离散的大脑区域使用微透析采样并同时记录。皮层电图 (ECoG) 活动可探测与癫痫发作相关的大脑化学和电图活动变化，这将使我们能够将生物标志物水平与癫痫发作活动相关联，并将用于在诱导之前、期间和之后持续监测多种生化途径。微透析实验将提供有关癫痫引起的氧化应激以及大脑对其反应的时间和空间信息，这种双重方法将使我们能够解决使用血浆和尿液采样以及标准组织采样技术仍不清楚的问题。 PI实验室先前开发的方法将用于监测ROS的形成、DNA损伤的生物标志物以及神经递质氨基酸和儿茶酚胺，并将开发新的分析方法来监测通过脂质过氧化、内源性硫醇和参与保护的二硫化物产生的醛。 ROS 和花生四烯酸代谢产生的前列腺素最初，我们将使用 3-巯基丙酸化学诱导的癫痫模型。 (3-MPA) 结合先进的分析方法和微透析采样，我们将研究从癫痫发作到氧化应激的神经事件，特别是氧化应激（通过 ROS 形成测量）和神经兴奋之间的时间关系。通过 GABA/谷氨酸比率和儿茶酚胺测量）将被确定并与癫痫发作的持续时间和强度相关。