Related Experiment Video
Updated: Nov 9, 2025
Assessing Neuroprotective Effects of Glycyrrhizae Radix et Rhizoma Extract Using a Transient Middle Cerebral Artery Occlusion Mouse Model
Published on: December 9, 2018
Agomelatine prevents macrophage infiltration and brain endothelial cell damage in a stroke mouse model
Yiqiang Cao1, Fei Wang1, Yonggang Wang1
1Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
Background And Purpose:
Ischemic/reperfusions are regarded as the clinical consensus for stroke treatment, which results in secondary injury of brain tissues. Increased blood-brain barrier (BBB) permeability and infiltration of inflammatory cells are responsible for the ischemic/reperfusion injury. In the present study, we aimed to investigate the effects of Agomelatine on brain ischemic/reperfusions injury and the underlying mechanism.
Methods:
MCAO model was established in mice. The expressions of CD68 and claudin-5 in the cerebral cortex were determined using an immunofluorescence assay. Brain permeability was evaluated using Evans blue staining assay. A two-chamber and two-cell trans-well assay was used to detect the migration ability of macrophages through endothelial cells. The expression levels of claudin-5 and MCP-1 in the endothelial cells were determined using qRT-PCR and ELISA.
Results:
CD68 was found to be up-regulated in the cerebral cortex of MCAO mice but was down-regulated by treatment with Agomelatine. The expression level of down-regulated claudin-5 in the cerebral cortex of MCAO mice was significantly suppressed by Agomelatine. Deeper staining of Evans blue was found in the MCAO group, which was however faded significantly in the Agomelatine treated MCAO mice. The migrated macrophages were significantly increased by hypoxia incubation but were greatly suppressed by the introduction of Agomelatine. The down-regulated claudin-5 by hypoxic incubation in endothelial cells was up-regulated by treatment with Agomelatine. Furthermore, the increased expression of MCP-1 in endothelial cells under hypoxic conditions was significantly inhibited by Agomelatine.
Conclusion:
Agomelatine prevents macrophage infiltration and brain endothelial cell damage in a stroke mouse model.
Insights
Agomelatine treatment reduced inflammatory cell infiltration and protected brain endothelial cells in a stroke model. This study investigated Agomelatine's effects on ischemic/reperfusion injury, showing its therapeutic potential.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Ischemic/reperfusion injury exacerbates stroke, causing secondary brain damage.
- Increased blood-brain barrier (BBB) permeability and inflammatory cell infiltration contribute to this injury.
- Understanding mechanisms to mitigate secondary injury is crucial for stroke treatment.
Purpose of the Study:
- To investigate the therapeutic effects of Agomelatine on brain ischemic/reperfusion injury.
- To elucidate the underlying mechanisms of Agomelatine's action in a stroke model.
Main Methods:
- A middle cerebral artery occlusion (MCAO) mouse model was established.
- Immunofluorescence, Evans blue staining, and trans-well assays were used to assess BBB integrity, inflammation, and cell migration.
- Quantitative real-time PCR (qRT-PCR) and ELISA measured specific protein and gene expression levels.
Main Results:
- Agomelatine downregulated CD68 (macrophage marker) and upregulated claudin-5 (BBB tight junction protein) in the cerebral cortex.
- Evans blue staining indicated reduced BBB permeability in Agomelatine-treated mice.
- Agomelatine suppressed macrophage migration and MCP-1 expression while restoring claudin-5 in endothelial cells under hypoxic conditions.
Conclusions:
- Agomelatine demonstrates a protective effect against brain ischemic/reperfusion injury.
- The drug prevents macrophage infiltration and mitigates damage to brain endothelial cells.
- Agomelatine shows promise as a therapeutic agent for stroke by preserving BBB integrity and reducing neuroinflammation.
