Isoflurane alleviates systemic inflammation-induced neuroinflammation by decreasing the blood-brain barrier's damage and regulating the microglia's polarization

Abstract

Abstract Background The fundamental pathological role of neuroinflammation is caused by the overactivation of microglia cells in various neurological diseases. Isoflurane has been shown to alleviate neuroinflammation and plays a neuroprotective role in cerebral ischemia-reperfusion, but its role in systemic inflammation remains unclear. This study investigated the role and potential mechanism of isoflurane in neuroinflammation induced by systemic inflammation. Methods Mice were injected with LPS intraperitoneally as the animal model. The cell models were BV2 microglia treated directly with LPS and HT22 neurons treated with the conditioned medium. FCM, IF, IHF, and other methods were used to explore the polarization state of microglia by comparing the effects of minocycline and blockers. WB, qPCR, and other methods were used to reveal the molecular mechanism. Results In this study, systemic inflammation triggers neuroinflammation, microglia activation, and neuronal impairment one day after modeling. Isoflurane attenuates brain edema, immune cell infiltration, and microglia activation by decreasing blood-brain barrier deterioration. In addition, isoflurane plays a neuroprotective role by regulating microglia polarization and inhibiting neuroinflammation. Simultaneously, data collected from in vitro cell experiments support the above findings. Conclusion These data prove that isoflurane plays a protective role in alleviating blood-brain barrier damage and regulating microglial cell polarization by signal axis to alleviate neuronal damage.