PUBLICATION
Sevoflurane postconditioning ameliorates cerebral hypoxia/reoxygenation injury in zebrafish involving the Akt/GSK-3β pathway activation and the microtubule-associated protein 2 promotion
- Authors
- Zhang, L., Yang, M., Wang, Z., Fan, D., Shen, F., Zou, X., Zhang, X., Hu, S., Hu, B., Hu, X.
- ID
- ZDB-PUB-240505-1
- Date
- 2024
- Source
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 175: 116693116693 (Journal)
- Registered Authors
- Hu, Bing
- Keywords
- Cerebral hypoxia/reoxygenation injury, Cerebral protection, MAP2, Sevoflurane postconditioning, Zebrafish
- MeSH Terms
-
- Animals
- Apoptosis/drug effects
- Disease Models, Animal
- Glycogen Synthase Kinase 3 beta*/metabolism
- Hypoxia-Ischemia, Brain/drug therapy
- Hypoxia-Ischemia, Brain/metabolism
- Hypoxia-Ischemia, Brain/pathology
- Ischemic Postconditioning/methods
- Male
- Microtubule-Associated Proteins*/metabolism
- Mitochondria/drug effects
- Mitochondria/metabolism
- Neuroprotective Agents*/pharmacology
- Proto-Oncogene Proteins c-akt*/metabolism
- Reperfusion Injury/drug therapy
- Reperfusion Injury/metabolism
- Reperfusion Injury/pathology
- Sevoflurane*/pharmacology
- Signal Transduction*/drug effects
- Zebrafish*
- Zebrafish Proteins/metabolism
- PubMed
- 38701566 Full text @ Biomed. Pharmacother.
Citation
Zhang, L., Yang, M., Wang, Z., Fan, D., Shen, F., Zou, X., Zhang, X., Hu, S., Hu, B., Hu, X. (2024) Sevoflurane postconditioning ameliorates cerebral hypoxia/reoxygenation injury in zebrafish involving the Akt/GSK-3β pathway activation and the microtubule-associated protein 2 promotion. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 175:116693116693.
Abstract
Sevoflurane postconditioning has been shown to provide neuroprotection against cerebral hypoxia-ischemia injury, but the mechanisms remain elusive. Microtubule-associated protein 2 (MAP2) is implicated in early neuronal hypoxia-ischemia injury. This study aimed to investigate whether the neuroprotective effects of sevoflurane postconditioning are related to the Akt/GSK-3β pathway and its downstream target MAP2 in zebrafish hypoxia/reoxygenation (H/R) model. Sevoflurane postconditioning or GSK-3β inhibitor TDZD-8 were used to treat H/R zebrafish. The cerebral infarction, neuronal apoptosis, and mitochondrial changes were evaluated using TTC staining, TUNEL staining, and transmission electron microscopy, respectively. The distribution of MAP2 in the brain was determined by immunofluorescence imaging. The levels of Akt, p-Akt, GSK-3β, p-GSK-3β, and MAP2 proteins were evaluated by Western blotting. The neurobehavioral recovery of zebrafish was assessed based on optokinetic response behavior. Our results indicated that sevoflurane postconditioning and TDZD-8 significantly reduced the cerebral infarction area, suppressed cell apoptosis, and improved mitochondrial integrity in zebrafish subjected to H/R. Furthermore, sevoflurane postconditioning and TDZD-8 elevated the ratios of p-Akt/Akt and p-GSK-3β/GSK-3β. However, the neuroprotective effect of sevoflurane postconditioning was effectively abolished upon suppression of MAP2 expression. In conclusion, sevoflurane postconditioning ameliorated cerebral H/R injury and facilitated the restoration of neurobehavioral function through the activation of Akt/GSK-3β pathway and promotion of MAP2 expression.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping