PUBLICATION
Therapeutic Effects of Iron Chelation in Atorvastatin-Induced Intracranial Hemorrhage of Zebrafish Larvae
- Authors
- Nakamura, S., Saito, Y., Gouda, T., Imai, T., Shimazawa, M., Nishimura, Y., Hara, H.
- ID
- ZDB-PUB-201020-46
- Date
- 2020
- Source
- Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 29: 105215 (Journal)
- Registered Authors
- Nishimura, Yuhei
- Keywords
- Atorvastatin (ATV), Cerebral hemorrhage, Iron chelator, Zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Apoptosis/drug effects
- Atorvastatin
- Brain/drug effects*
- Brain/embryology
- Deferasirox/pharmacology*
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Intracranial Hemorrhages/chemically induced
- Intracranial Hemorrhages/embryology
- Intracranial Hemorrhages/prevention & control*
- Iron Chelating Agents/pharmacology*
- Larva
- Time Factors
- Zebrafish/embryology
- Zebrafish/genetics
- PubMed
- 33066911 Full text @ J Stroke Cerebrovasc Dis
Citation
Nakamura, S., Saito, Y., Gouda, T., Imai, T., Shimazawa, M., Nishimura, Y., Hara, H. (2020) Therapeutic Effects of Iron Chelation in Atorvastatin-Induced Intracranial Hemorrhage of Zebrafish Larvae. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. 29:105215.
Abstract
Objective Intracranial hemorrhage (ICH) catastrophically damages the cerebral vasculature, and severely compromises blood-brain barrier (BBB) function. The prognosis of ICH is poor due to the drastic and rapid progression of its pathology, and the lack of effective treatments presents a significant unmet clinical need. The present paper provides several evidences about the relationship between ICH bleeding status and mortality and the potential therapeutic effects of an iron chelator for ICH.
Methods Zebrafish are a highly transparent animal model, allowing live imaging of the complex cerebral vasculature. Thus, to further elucidate ATV-induced ICH, we investigated the concentration- and time-dependent phenotypes of ATV-induced ICH with zebrafish larvae.
Results The effects of ATV on mortality and ICH incidence in zebrafish larvae were concentration-dependent. Further, ATV treatment decreased vascular density of the hindbrain in a concentration-dependent manner, and hematoma volume was inversely correlated with ATV concentration. The number of cranial TUNEL-positive apoptotic cells was markedly increased 3 days post-fertilization. Importantly, the iron chelator deferasirox (DFR) decreased the incidence of ATV-induced ICH in zebrafish larvae.
Conclusion These findings provided insight into the pathology and regulatory mechanism of ATV-induced ICH, and demonstrated the therapeutic effects of iron chelators.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping