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Sevoflurane protects against intracerebral hemorrhage via microRNA-133b/FOXO4/BCL2 axis
Lei Li1, Yanping Zhan1, Haimei Xia1
1Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.
Abstract:
The application of Sevoflurane (Sev) in neurological diseases has been documented. We herein clarified the role of Sev in intracerebral hemorrhage (ICH). Through bioinformatics analysis, ICH-related microRNA (miRNA) was collected with microRNA-133b (miR-133b) chosen for the study subject. Then, the related downstream gene Forkhead box O4 (FOXO4) was identified. For in vivo assays, an ICH mouse model was established by autologous blood injection. For in vitro assays, hippocampal neurons were extracted from mouse brain tissues, and erythrocyte lysates were employed to simulate in vitro hemorrhage. Interaction between miR-133b and FOXO4 as well as between FOXO4 and BCL2 were assayed. We found decreased miR-133b in the brain tissue of ICH mice and erythrocyte lysate-treated hippocampal neurons. Sev treatment attenuated ICH and hippocampal neuronal apoptosis in mice by upregulating miR-133b. miR-133b targeted FOXO4 expression, and inhibition of FOXO4 attenuated hippocampal neuronal apoptosis by increasing BCL2 expression. Sev attenuated ICH in mice by increasing BCL2 expression through regulation of miR-133b-mediated FOXO4 expression. The findings highlighted the protective effect of Sev on ICH mice through the regulation of miR-133b-mediated FOXO4 expression.
Insights
Sevoflurane (Sev) protects against intracerebral hemorrhage (ICH) by upregulating microRNA-133b (miR-133b). This mechanism involves inhibiting FOXO4, thereby increasing BCL2 expression and reducing neuronal apoptosis in ICH mouse models.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Intracerebral hemorrhage (ICH) is a severe neurological condition with limited treatment options.
- Sevoflurane (Sev) has shown potential in neurological applications, but its specific role in ICH requires elucidation.
Purpose of the Study:
- To investigate the protective effects and underlying molecular mechanisms of Sevoflurane in intracerebral hemorrhage.
- To identify key microRNAs and their downstream targets involved in Sevoflurane's action on ICH.
Main Methods:
- Bioinformatics analysis to identify ICH-related microRNAs, focusing on microRNA-133b (miR-133b) and its target Forkhead box O4 (FOXO4).
- Establishment of an in vivo ICH mouse model via autologous blood injection.
- In vitro assays using primary hippocampal neurons treated with erythrocyte lysates to simulate hemorrhage.
Main Results:
- Decreased levels of miR-133b were observed in ICH mouse brains and in vitro models.
- Sevoflurane treatment upregulated miR-133b, attenuating ICH and hippocampal neuronal apoptosis.
- miR-133b directly targets FOXO4; inhibition of FOXO4 increased BCL2 expression, reducing apoptosis.
Conclusions:
- Sevoflurane exerts a protective effect in intracerebral hemorrhage by modulating the miR-133b/FOXO4 pathway.
- Sevoflurane increases BCL2 expression via miR-133b-mediated regulation of FOXO4, thereby protecting against neuronal apoptosis in ICH.
