Edaravone dexborneol alleviates ischemic injury and neuroinflammation by modulating microglial and astrocyte polarization while inhibiting leukocyte infiltration

•The present study demonstrated EDB significantly reduced the brain infarction and improved long-term sensorimotor function after stroke.•EDB alleviated the MCAO-induced neuroinflammation by restraining the polarization of microglia and astrocyte toward proinflammatory phenotype and inhibiting the production of proinflammatory cytokines (such as IL-1β, TNF-α, and IL-6) and chemokines (including MCAP-1 and CXCL1)•EDB ameliorated MCAO-induced BBB disruption by suppressing the degradation of tight junction protein and attenuated the accumulation of peripheral leukocytes in the ischemic brain.•Systemic EDB administration inhibited the macrophage phenotypic shift toward the M1 phenotype and the macrophage-dependent inflammatory response in the spleen and blood. Poststroke inflammation is essential in the mechanism of secondary injury, and it is orchestrated by resident microglia, astrocytes, and circulating immune cells. Edaravone dexborneol (EDB) is a combination of edaravone and borneol that has been identified as a clinical protectant for stroke management. In this study, we verified the anti-inflammatory effect of EDB in the mouse model of ischemia and investigated its modulatory action on inflammation-related cells. C57BL/6 male mice, which had the transient middle cerebral artery occlusion (tMCAO), were treated (i.p.) with EDB (15 mg/kg). EDB administration significantly reduced the brain infarction and improved the sensorimotor function after stroke. And EDB alleviated the neuroinflammation by restraining the polarization of microglia/macrophages and astrocyte toward proinflammatory phenotype and inhibiting the production of proinflammatory cytokines (such as IL-1β, TNF-α, and IL-6) and chemokines (including MCP-1 and CXCL1). Furthermore, EDB ameliorated the MCAO-induced impairment of Blood–brain barrier (BBB) by suppressing the degradation of tight junction protein and attenuated the accumulation of peripheral leukocytes in the ischemic brain. Additionally, systemic EDB administration inhibited the macrophage phenotypic shift toward the M1 phenotype and the macrophage-dependent inflammatory response in the spleen and blood. Collectively, EDB protects against ischemic stroke injury by inhibiting the proinflammatory activation of microglia/macrophages and astrocytes and through reduction by invasion of circulating immune cells, which reduces central and peripheral inflammation following stroke.