In Vivo Zebrafish GFAP ELISA for Neurotoxicity

体内斑马鱼 GFAP ELISA 检测神经毒性

• 批准号: 7482582
• 负责人: Chunqi Li
• 金额: $ 20.31万
• 依托单位: PHYLONIX PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-17 至 2010-05-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7482582
• 关键词: Adverse effects; Aftercare; Angiogenesis Inhibitors; Animal Model; Animals; Antigens; Astrocytes; Biological Assay; Brain; Brain Injuries; Brain Part; Cardiovascular system; Cells; Cessation of life; Characteristics; Class; Complex; Condition; Development; Dose; Drug Delivery Systems; Embryo; Environment; Enzyme-Linked Immunosorbent Assay; Evaluation; Exhibits; Fertilization; Genes; Glial Fibrillary Acidic Protein; Government; Guidelines; Hand; Hour; Human; Immunoassay; Intermediate Filament Proteins; Ischemic Stroke; Link; Maintenance; Mammals; Methods; Monoclonal Antibodies; Mus; Nervous System Physiology; Nervous system structure; Neurodegenerative Disorders; Neuroglia; Neurons; Neurotoxins; Numbers; Performance; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase I Clinical Trials; Physiological; Preclinical Drug Evaluation; Procedures; Process; Proteins; Purpose; Reaction; Research; SU 5416; Safety; Screening procedure; Sensitivity and Specificity; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Solid; Spinal Cord; Staining method; Stains; Standards of Weights and Measures; Statistically Significant; Sterility; Structure; Students; Techniques; Testing; Tetrachlorodibenzodioxin; Therapeutic; Time; Toxic effect; Toxicity Tests; Zebrafish; astrogliosis; base; behavior test; brain tissue; concept; cost; day; drug withdrawal; in vivo; milliliter; neurotoxic; neurotoxicity; protein expression; response; size; tumor

DESCRIPTION (provided by applicant): Toxic damage to the nervous system results in direct damage/death of neurons and glial cells. Since drug reaction varies with type of neuron, neurotoxicity assays based on the characteristics of one type of neuron do not necessarily predict the effect of different drug classes on other types of neurons. Glial cells, on the other hand, support all neurons, and activation of astrocytes, a type of glial cells, (astrogliosis) has been linked with every form of brain injury, including: drug-induced neurotoxicity, ischemic stroke, neurodegenerative disease, and tumors. Using zebra fish, this SBIR proposes to develop a rapid in vivo assay for assessing drug induced neurotoxicity. Zebra fish is a good animal model for toxicity testing. Development of the zebra fish CNS has been extensively studied and many regulatory and morphological features are highly conserved. The zebra fish assay permits evaluation of the therapeutic potential of a compound in a complex physiological environment using throughput similar to cell-based assays. Using cell-based screens, this information is impossible to obtain. Additional advantages of the zebra fish assay include: assay time and cost, ease of embryo maintenance during drug delivery, compatibility of assay procedures with standard microplate formats, single drug dosing for each embryo, and the ability to test large numbers of embryos for statistically significant results.

描述（由申请人提供）：对神经系统的毒性损伤导致神经元和神经胶质细胞的直接损伤/死亡。由于药物反应因神经元类型而异，因此基于一种类型神经元特征的神经毒性测定不一定能预测不同药物类别对其他类型神经元的影响。另一方面，神经胶质细胞支持所有神经元，星形胶质细胞（一种神经胶质细胞）的激活（星形胶质细胞增生）与各种形式的脑损伤有关，包括：药物引起的神经毒性、缺血性中风、神经退行性疾病和肿瘤。该 SBIR 提议使用斑马鱼开发一种快速体内测定法来评估药物引起的神经毒性。斑马鱼是毒性测试的良好动物模型。斑马鱼中枢神经系统的发育已被广泛研究，许多调节和形态特征高度保守。斑马鱼测定可以使用类似于细胞测定的通量来评估化合物在复杂生理环境中的治疗潜力。使用基于细胞的屏幕，无法获得此信息。斑马鱼检测的其他优点包括：检测时间和成本、药物输送过程中胚胎维护的简便性、检测程序与标准微孔板格式的兼容性、每个胚胎的单一药物剂量以及测试大量胚胎的统计显着性的能力结果。