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Intraluminal Middle Cerebral Artery Occlusion MCAO Model for Ischemic Stroke with Laser Doppler Flowmetry Guidance in Mice
Published on: May 8, 2011
Sevoflurane protects mice from cerebral ischaemic injury by regulating microRNA-203-3p/HDAC4/Bcl-2 axis
Jie Song1, Ke He2, Longqiu Yang2,3
1Department of Anesthesiology, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China.
Abstract:
Sevoflurane (Sevo) is neuroprotective in ischaemic injury, but its specific mechanism in the disease from microRNA-203-3p/histone deacetylases 4/B-cell lymphoma 2 (miR-203-3p/HDAC4/Bcl-2) axis asks for a comprehensive explanation. A middle cerebral artery occlusion (MCAO) mouse model was established by nylon suture method. miR-203-3p and HDAC4 expression was measured in mouse brain tissues. The MCAO mice were exposed to Sevo or injected with miR-203-3p- or HDAC4-related plasmids. In response to Sevo treatment or plasmid interference, neurological function, brain pathology, neuronal apoptosis and inflammation were determined. The interactions of miR-203-3p and HDAC4, and HDAC4 and Bcl-2 were verified. MCAO mice presented down-regulated miR-203-3p and up-regulated HDAC4. Sevo improved neurological function, brain pathological damage and reduced neuronal apoptosis and inflammation in MCAO mice, while overexpressing miR-203-3p further enhanced those effects. HDAC4 overexpression antagonized the impacts of miR-203-3p up-regulation on MCAO mice. The targeting relation existed between miR-203-3p and HDAC4, as well as between HDAC4 and Bcl-2. It is clearly elucidated that miR-203-3p enhances the protective effects of Sevo on MCAO mice through elevating Bcl-2 and down-regulating HDAC4, potentially and clinically offering an effective treatment method with Sevo for cerebral ischaemic injury.
Insights
Sevoflurane protects the brain from ischemic injury by regulating the microRNA-203-3p/histone deacetylases 4/B-cell lymphoma 2 pathway. This mechanism enhances neuroprotection and reduces brain damage in ischemic stroke models.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Sevoflurane (Sevo) demonstrates neuroprotective properties against ischemic injury.
- The precise molecular mechanisms underlying sevoflurane's neuroprotection, particularly involving the microRNA-203-3p/histone deacetylases 4/B-cell lymphoma 2 (miR-203-3p/HDAC4/Bcl-2) axis, require comprehensive elucidation.
Purpose of the Study:
- To investigate the specific mechanism of sevoflurane's neuroprotection in cerebral ischemic injury.
- To explore the role of the miR-203-3p/HDAC4/Bcl-2 axis in sevoflurane's therapeutic effects.
Main Methods:
- Establishment of a middle cerebral artery occlusion (MCAO) mouse model.
- Measurement of miR-203-3p and HDAC4 expression in brain tissues.
- Administration of sevoflurane or related plasmids (miR-203-3p, HDAC4) to MCAO mice.
- Assessment of neurological function, brain pathology, neuronal apoptosis, and inflammation.
- Verification of molecular interactions between miR-203-3p, HDAC4, and Bcl-2.
Main Results:
- MCAO mice exhibited decreased miR-203-3p and increased HDAC4 expression.
- Sevoflurane treatment improved neurological function, reduced brain damage, neuronal apoptosis, and inflammation in MCAO mice.
- Overexpression of miR-203-3p potentiated sevoflurane's protective effects, while HDAC4 overexpression antagonized these effects.
- Direct targeting interactions were confirmed between miR-203-3p and HDAC4, and between HDAC4 and Bcl-2.
Conclusions:
- Sevoflurane enhances neuroprotection in MCAO mice by upregulating miR-203-3p, which in turn downregulates HDAC4 and elevates Bcl-2 expression.
- The miR-203-3p/HDAC4/Bcl-2 pathway is a key mechanism mediating sevoflurane's protective effects against cerebral ischemic injury.
- This study provides a mechanistic basis for the clinical application of sevoflurane as a treatment for cerebral ischemic injury.
