Establishing a high throughput drug screening system for cerebral ischemia using zebrafish larvae

• Published in: Journal of pharmacological sciences Vol. 147; no. 1; pp. 138 - 142
• Main Authors: Matsumoto, Mami, Miyamoto, Moeri, Sawahata, Masahito, Izumi, Yasuhiko, Takada-Takatori, Yuki, Kume, Toshiaki
• Format: Journal Article
• Language: English
• Published: Japan Elsevier B.V 01.09.2021; Elsevier
• Subjects: Animals; Brain - pathology; Brain Ischemia - drug therapy; Brain Ischemia - etiology; Brain Ischemia - pathology; Cell Death - drug effects; Cerebral ischemia; Disease Models, Animal; Dizocilpine Maleate - pharmacology; Dizocilpine Maleate - therapeutic use; Drug Evaluation, Preclinical - methods; Drug screening; Edaravone - pharmacology; Edaravone - therapeutic use; Free Radical Scavengers - pharmacology; Free Radical Scavengers - therapeutic use; Gases; Hypoxia - complications; Hypoxia - pathology; Larva; N-methyl-D-aspartate (NMDA) receptor; Neurons - pathology; Nitrogen; Reactive oxygen species; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Zebrafish; N-methyl-D-aspartate (NMDA) receptor; Zebrafish; Cerebral ischemia; Reactive oxygen species; Drug screening
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1016/j.jphs.2021.06.006

We previously generated an ischemic stroke in a zebrafish model using N2 gas perfusion; however, this model was an unsuitable drug screening system due to low throughput. In this study, we examined a zebrafish ischemic stroke model using an oxygen absorber to assess drug effects. Hypoxic exposure more than 2 h using the oxygen absorber significantly induced cell death in the brain and damage to the neuronal cells. To confirm the utility of the ischemic model induced by the oxygen absorber, we treated zebrafish with neuroprotective agents. MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist, significantly suppressed cell death in the brain, and edaravone, a free radical scavenger, significantly reduced the number of dead cells. These results suggest that the activation of NMDA receptors and the production of reactive oxygen species induce neuronal cell damage in accordance with previous mammalian reports. We demonstrate the suitability of an ischemic stroke model in zebrafish larvae using the oxygen absorber, enabling a high throughput drug screening.