Neuronal ion and volume shifts after acute brain injury

急性脑损伤后神经元离子和体积变化

• 批准号: 10228299
• 负责人: Kevin J. Staley
• 金额: $ 12.43万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10228299
• 关键词: Acute Brain Injuries; Anticonvulsants; Apoptosis; Apoptotic; Applications Grants; Autopsy; Award; Biological Assay; Biological Markers; Caspase; Cell Death; Cells; Cellular Assay; Cessation of life; Data; Dyes; Electroencephalography; Epileptogenesis; Exposure to; Extinction (Psychology); Fluorescence; Funding; Future; Genetic; Grant; Histologic; Image; Individual; Injury; Intervention; Investigational Therapies; Ions; Isoflurophate; Label; Measures; Methods; Microglia; Monitor; Mus; Necrosis; Neonatal Brain Injury; Neurological outcome; Neurons; Neurosciences; Organophosphates; Paper; Pathway interactions; Population; Postdoctoral Fellow; Predictive Value; Predisposition; Progress Reports; Proteins; Publishing; Resolution; Role; Seizures; Source; Stains; Status Epilepticus; Testing; Time; Toxic effect; Transgenic Organisms; base; experience; experimental study; fluoro jade; improved; in vivo; mouse model; neuron loss; neuronal patterning; neuropathology; neurotoxic; neurotoxicity; novel; organophosphate poisoning; parent grant; protein expression; recombinase-mediated cassette exchange; resilience; selective expression; time use; treatment strategy; two-photon

PROPOSAL ABSTRACT We propose to test the accuracy and feasibility of a new, time-resolved measure of cell death after organophosphate (OP) poisoning in a murine model of OP-induced status epilepticus. This novel assay was developed as part of the grant, “Mechanisms of cell death during epileptogenesis”, a 7- year R37 (Javits Award) project. We hypothesize that single-timepoint assays of cell death after OP poisoning are not accurate because they cannot determine 1) how many cells have already undergone necrosis and are no longer visible, 2) how many cells have irreversibly committed to apoptotic death but are not yet positive for biomarkers of that pathway, and 3) how many cells have already undergone apoptotic death and have been phagocytosed by microglia so that they are no longer visible. We propose to measure cell death by the transgenic fluorescent protein quenching assay before and after OP poisoning to determine both the extent and the timing of neuronal death. These studies will form critical preliminary data for subsequent rigorous studies measuring the causative role of seizures in neuronal death and the neuroprotective value of various anticonvulsant and other treatment strategies after OP poisoning.

建议书摘要 我们建议测试一种新的、时间分辨的细胞死亡测量方法的准确性和可行性 有机磷(OP)中毒诱发癫痫持续状态的小鼠模型。这部小说 化验是作为“癫痫发生过程中细胞死亡机制”资助的一部分而开发的，一个7- R37年(贾维茨奖)项目。我们假设手术后细胞死亡的单时间点分析 中毒并不准确，因为他们无法确定1)已经有多少细胞 经历了坏死并不再可见，2)有多少细胞不可逆转地致力于 凋亡性死亡，但尚未对该途径的生物标志物呈阳性，以及3)有多少细胞 已经经历了凋亡性死亡，并被小胶质细胞吞噬，因此它们不是 更长的可见度。我们建议用转基因荧光蛋白来测量细胞死亡。 OP中毒前后的猝灭试验以确定中毒的程度和时间 神经元死亡。这些研究将为随后的严格研究形成关键的初步数据 测定癫痫发作在神经元死亡中的作用以及不同药物的神经保护价值 OP中毒后抗惊厥药物及其他治疗策略。