Edaravone Alleviates BV-2 Microglia-Mediated Neuroinflammation Through the PI3K/AKT/ NF-κB Pathway.

Abstract

Ischemic stroke (IS) poses a significant threat to human health. Research has demonstrated that microglia (MG)-mediated neuroinflammatory responses play a crucial role in the pathogenesis of IS. Consequently, inhibiting MG activation and reducing the inflammatory response may be key strategies for the clinical treatment of stroke and neurodegenerative diseases. Edaravone (EDA), a potent anti-inflammatory and antioxidant, is currently used in the clinical treatment of IS; however, its anti-inflammatory mechanisms remain inadequately understood. To address this, network pharmacology (NP) analysis is employed to identify the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway as a potential mediator of the inflammatory response triggered by activated microglia following EDA treatment. In vitro oxygen-glucose deprivation (OGD) is used to induce BV-2 MG activation, and an in vivo middle cerebral artery occlusion (MCAO) mouse model is established. Western blot and immunofluorescence staining are used to detect changes in the phosphorylation levels of pathway-related proteins and the expression of inflammatory factors. Additionally, the PI3K pathway inhibitor LY294002 and a PI3K overexpression plasmid are introduced to further analyze the expression changes of these markers. The results suggest that EDA may alleviate the inflammatory response mediated by activated MG through the PI3K/Akt signaling pathway.