RRC ID 70450
Author Matsumoto M, Miyamoto M, Sawahata M, Izumi Y, Takada-Takatori Y, Kume T.
Title Establishing a high throughput drug screening system for cerebral ischemia using zebrafish larvae.
Journal J Pharmacol Sci
Abstract 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.
Volume 147(1)
Pages 138-142
Published 2021-9-1
DOI 10.1016/j.jphs.2021.06.006
PII S1347-8613(21)00062-1
PMID 34294365
MeSH Animals Brain / pathology Brain Ischemia / drug therapy* Brain Ischemia / etiology Brain Ischemia / pathology Cell Death / drug effects Disease Models, Animal Dizocilpine Maleate / pharmacology Dizocilpine Maleate / therapeutic use* Drug Evaluation, Preclinical / methods* Edaravone / pharmacology Edaravone / therapeutic use* Free Radical Scavengers / pharmacology Free Radical Scavengers / therapeutic use* Gases Hypoxia / complications Hypoxia / pathology Larva* Neurons / pathology Nitrogen Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors* Zebrafish*
IF 2.835
Zebrafish Tg(Huc:Kaede)rw0130a