In Vivo Zebrafish GFAP ELISA for Neurotoxicity

描述(申请人提供)：神经系统的毒性损伤会导致神经元和神经胶质细胞的直接损伤/死亡。由于药物反应随神经元类型的不同而不同，基于一种神经元特征的神经毒性分析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，胶质细胞支持所有神经元，而星形胶质细胞的激活与各种形式的脑损伤有关，包括：药物所致的神经毒性、缺血性中风、神经退行性疾病和肿瘤。使用斑马鱼，这项SBIR建议建立一种快速的体内测试来评估药物引起的神经毒性。斑马鱼是一种很好的毒性测试动物模型。斑马鱼中枢神经系统的发育已经被广泛研究，许多调节和形态特征是高度保守的。斑马鱼试验允许在复杂的生理环境中使用类似于基于细胞的分析的吞吐量来评估化合物的治疗潜力。使用基于细胞的屏幕，这些信息是不可能获得的。斑马鱼检测的其他优势包括：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，以及能够测试大量胚胎以获得统计上显著的结果。

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.