Isoflurane postconditioning reduces ischemia-induced nuclear factor-[kappa]B activation and interleukin 1[beta] production to provide neuroprotection in rats and mice

Application of isoflurane, a volatile anesthetic, after brain ischemia can reduce ischemic brain injury in rodents (isoflurane postconditioning). This study is designed to determine whether isoflurane postconditioning improves long-term neurological outcome after focal brain ischemia and whether this protection is mediated by attenuating neuroinflammation. Adult male SpragueaDawley rats were subjected to a 90-min middle cerebral arterial occlusion (MCAO). Isoflurane postconditioning was performed by exposing rats to 2% isoflurane for 60 min immediately after the MCAO. Isoflurane postconditioning reduced brain infarct volumes, apoptotic cells in the ischemic penumbral brain tissues and neurological deficits of rats at 4 weeks after the MCAO. Isoflurane postconditioning reduced brain ischemia/reperfusion-induced nuclear transcription factor (NF)-[kappa]B (NF-[kappa]B) activation as well as interleukin 1[beta] (IL-1[beta]) and interleukin-6 production in the ischemic penumbral brain tissues at 24 h after the MCAO. IL-1[beta] deficient mice had smaller brain infarct volumes and better neurological functions than wild-type mice at 24 h after a 90-min focal brain ischemia. Isoflurane posttreatment failed to induce neuroprotection in the IL-1[beta] deficient mice. Our results suggest that isoflurane postconditioning improved long-term neurological outcome after transient focal brain ischemia. This protection may be mediated by inhibiting NF-[kappa]B activation and the production of the proinflammatory cytokine IL-1[beta].