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

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 mo...

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Bibliographic Details
Published in:Journal of pharmacological sciences 2021-09, Vol.147 (1), p.138-142
Main Authors: Matsumoto, Mami, Miyamoto, Moeri, Sawahata, Masahito, Izumi, Yasuhiko, Takada-Takatori, Yuki, Kume, Toshiaki
Format: Article
Language:English
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
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Summary: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.
ISSN:1347-8613
1347-8648
DOI:10.1016/j.jphs.2021.06.006