PUBLICATION
Ponatinib-induced ischemic stroke in larval zebrafish for drug screening
- Authors
- Zhu, X.Y., Xia, B., Ye, T., Dai, M.Z., Yang, H., Li, C.Q., Li, P.
- ID
- ZDB-PUB-200716-9
- Date
- 2020
- Source
- European Journal of Pharmacology 889: 173292 (Journal)
- Registered Authors
- Keywords
- Animal model, Drug screening, Ischemic stroke, Ponatinib, Zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Antineoplastic Agents/toxicity*
- Brain Ischemia/chemically induced*
- Brain Ischemia/diagnostic imaging
- Brain Ischemia/drug therapy
- Disease Models, Animal*
- Drug Evaluation, Preclinical/methods
- Imidazoles/toxicity*
- Ischemic Stroke/chemically induced*
- Ischemic Stroke/diagnostic imaging
- Ischemic Stroke/drug therapy
- Larva/drug effects*
- Platelet Aggregation Inhibitors/therapeutic use
- Pyridazines/toxicity*
- Zebrafish
- PubMed
- 32668288 Full text @ Eur. J. Pharmacol.
Citation
Zhu, X.Y., Xia, B., Ye, T., Dai, M.Z., Yang, H., Li, C.Q., Li, P. (2020) Ponatinib-induced ischemic stroke in larval zebrafish for drug screening. European Journal of Pharmacology. 889:173292.
Abstract
Conventional mammalian ischemic stroke models for drug screening are technically challenging, laborious and time-consuming. In this study, using Ponatinib as an inducer, we developed and characterized a zebrafish ischemic stroke model. This zebrafish ischemic stroke had the cerebral vascular endothelial injury, thrombosis, reduced blood flow, inflammation and apoptosis as well as the reduced motility. The zebrafish ischemic stroke model was validated with 6 known human therapeutic drugs of ischemic stroke (Aspirin, Clopidogrel, Naoxintong capsules, Edaravone, Xingnaojing injection, Shuxuening injection). The mRNA levels of the neovascularization-related gene (vegfaa) and vascular endothelial growth factor receptor gene (VEGFR), neurodevelopment related genes (mbp and α1-tubulin), brain-derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF) were significantly downregulated; whereas apoptosis-related genes (caspase-3, caspase-7, caspase-9 and bax/bcl-2), and inflammatory factor genes (IL-1β, IL-6, IL-10, TNF-α and NF-κB) were remarkably upregulated in the model. These results suggest that the pathophysiology of Ponatinib-induced zebrafish ischemic stroke is similar to that of human ischemic stroke patients and this whole animal model could be used to study the complex cellular and molecular pathogenesis of ischemic stroke and to rapidly identify therapeutic agents.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping