Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA.
Neurobiol Dis. 2013 Jun;54:216-24. doi: 10.1016/j.nbd.2012.12.014. Epub 2013 Jan 8.
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 Sprague-Dawley rats were subjected to a 90-min middle cerebral arterial occlusion (MCAO). Isoflurane postconditioning was performed by exposing rats to 2% isoflurane for 60min immediately after the MCAO. Isoflurane postconditioning reduced brain infarct volumes, apoptotic cells in the ischemic penumbral brain tissues and neurological deficits of rats at 4weeks after the MCAO. Isoflurane postconditioning reduced brain ischemia/reperfusion-induced nuclear transcription factor (NF)-κB (NF-κB) activation as well as interleukin 1β (IL-1β) and interleukin-6 production in the ischemic penumbral brain tissues at 24h after the MCAO. IL-1β deficient mice had smaller brain infarct volumes and better neurological functions than wild-type mice at 24h after a 90-min focal brain ischemia. Isoflurane posttreatment failed to induce neuroprotection in the IL-1β 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-κB activation and the production of the proinflammatory cytokine IL-1β.
异氟醚作为一种挥发性麻醉剂，在脑缺血后应用可以减轻啮齿动物的缺血性脑损伤（异氟醚后处理）。本研究旨在确定异氟醚后处理是否能改善局灶性脑缺血后的长期神经功能预后，以及这种保护作用是否通过减轻神经炎症来介导。成年雄性 Sprague-Dawley 大鼠接受 90 分钟大脑中动脉闭塞（MCAO）。MCAO 后立即用 2%异氟醚暴露大鼠 60 分钟，进行异氟醚后处理。异氟醚后处理减少了脑梗死体积、缺血半影区脑组织中的凋亡细胞和 MCAO 后 4 周时大鼠的神经功能缺损。异氟醚后处理减少了脑缺血再灌注诱导的核转录因子（NF）-κB（NF-κB）激活以及缺血半影区脑组织中白细胞介素 1β（IL-1β）和白细胞介素-6 的产生。在 90 分钟局灶性脑缺血后 24 小时，IL-1β 缺陷型小鼠的脑梗死体积较小，神经功能较好。IL-1β 缺陷型小鼠的异氟醚后处理未能诱导神经保护。我们的结果表明，异氟醚后处理改善了短暂性局灶性脑缺血后的长期神经功能预后。这种保护作用可能是通过抑制 NF-κB 激活和促炎细胞因子 IL-1β 的产生来介导的。
