2. Academic Validation
  3. Ponatinib-induced ischemic stroke in larval zebrafish for drug screening

Ponatinib-induced ischemic stroke in larval zebrafish for drug screening

  • Eur J Pharmacol. 2020 Dec 15;889:173292. doi: 10.1016/j.ejphar.2020.173292.
Xiao-Yu Zhu 1,  Bo Xia 2,  Ting Ye 2,  Ming-Zhu Dai 2,  Hua Yang 3,  Chun-Qi Li 4,  Ping Li 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, PR China; Hunter Biotechnology, Inc, F1A, Building 5, No. 88 Jiangling Road, Binjiang Zone, Hangzhou City, Zhejiang Province, 310051, PR China.
  • 2 Hunter Biotechnology, Inc, F1A, Building 5, No. 88 Jiangling Road, Binjiang Zone, Hangzhou City, Zhejiang Province, 310051, PR China.
  • 3 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, PR China.
  • 4 Hunter Biotechnology, Inc, F1A, Building 5, No. 88 Jiangling Road, Binjiang Zone, Hangzhou City, Zhejiang Province, 310051, PR China. Electronic address: jackli@zhunter.com.
  • 5 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, PR China. Electronic address: liping2004@126.com.
PMID: 32668288 DOI: 10.1016/j.ejphar.2020.173292
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.

Keywords

Animal model; Drug screening; Ischemic stroke; Ponatinib; Zebrafish.

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