Objective Sevoflurane preconditioning has been demonstrated to reduce cerebral ischemia–reperfusion（IR） injury,but the underlying mechanisms have not been fully elucidated.Besides,different protocols would usually lead to different results.The objective of this study was to determine whether dual exposure to sevoflurane improves the effect of anesthetic preconditioning against oxygen and glucose deprivation（OGD）injury in vitro.Methods Rat hippocampal slices under normoxic conditions（95%O2/5%CO2）were pre-exposed to sevoflurane 1,2 and 3 minimum alveolar concentration （MAC）for 30 min,once or twice,with 15-min washout after each exposure.The slices were then subjected to 13-min OGD treatment（95%N2/5%CO2,glucose-free）,followed by 30-min reoxygenation.The population spikes（PSs）were recorded in the CA1 region of rat hippocampus.The percentage of PS amplitude at the end of 30-min reoxygenation to that before OGD treatment was calculated,since it could indicate the recovery degree of neuronal function.In addition,to assess the role of mitogen-activated protein kinases（MAPKs）in preconditioning,U0126,an inhibitor of extracellular signal–regulated protein kinase（MEK-ERK1/2,ERK1/2 MAPK）,and SB203580,an inhibitor of p38 MAPK,were separately added 10 min before sevoflurane exposure.Results Preconditioning once with sevoflurane 1,2,and 3 MAC increased the percentage of PS amplitude at the end of 30-min reoxygenation to that before OGD treatment,from（15.13±3.79）%（control）to（31.88±5.36）%, （44.00±5.01）%,and（49.50±6.25）%,respectively,and twice preconditioning with sevoflurane 1,2,and 3 MAC increased the percentage to（38.53±4.36）%,（50.74±7.05）%and（55.86±6.23）%,respectively.The effect of duplicate preconditioning with sevoflurane 3 MAC was blocked by U0126[（16.23±4.62）%].Conclusion Sevoflurane preconditioning can induce neuroprotection against OGD injury in vitro,and preconditioning twice enhances this effect.Besides,the activation of extracellular signal
