Abstract
Cerebral ischemic stroke is one of the main causes of death and long-term disability worldwide. However, the mechanism is unclear, and treatments are limited. In this study, we aimed to investigate the anti-inflammatory effect of agomelatine in a permanent middle cerebral artery occlusion (pMCAO) model. Forty-eight male Wistar rats were randomly divided into four groups: sham, pMCAO + vehicle, pMCAO + agomelatine (40 mg/kg, i.p.), and pMCAO + melatonin (10 mg/kg, i.p.) groups. On day 1 after permanent cerebral ischemia, the animals were sacrificed, and brain tissues were collected for western blot analysis, and immunohistochemistry. Agomelatine treatment ameliorated inflammatory responses by decreasing the protein levels of trigger Toll-like receptor (TLR4)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway components together with nucleotide-binding domain, leucine-rich-containing family, pyrin domain–containing-3 (NLRP3) inflammasome components. In addition, agomelatine suppressed microglial activation and pyroptotic cell death after cerebral ischemic injury. These results suggest that agomelatine exerts an anti-inflammatory effect and attenuates brain damage by inhibiting microglial activation through the TLR4/NLRP3 signaling pathway.
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Funding
This work was supported by the Thailand Research Fund (grant number RSA6080025 to JT) and the Royal Golden Jubilee (PHD/0018/2559 WC; PHD/0011/2558 SK). This work was partially supported by Center for Research and Development of Natural Products for Health, Chiang Mai University.
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Conceptualization: WC JT. Data curation: WC SK JT. Funding acquisition: JT. Investigation: WC SK CT. Methodology: WC SK CT JT. Project administration: JT. Resources: PG JT. Visualization: WC JT. Writing—original draft: WC PG JT.
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Chumboatong, W., Khamchai, S., Tocharus, C. et al. Agomelatine Exerts an Anti-inflammatory Effect by Inhibiting Microglial Activation Through TLR4/NLRP3 Pathway in pMCAO Rats. Neurotox Res 40, 259–266 (2022). https://doi.org/10.1007/s12640-021-00447-6
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DOI: https://doi.org/10.1007/s12640-021-00447-6