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. ? ? ?
