Objective To test the ability of isoflurane-induced preconditioning against oxygen and glucose deprivation (OGD) injury in vitro. Methods Rat hippocampal slices were exposed to 1 volume percentage (vol%)

2vol% or 3vol% isoflurane respectively for 20 minutes under normoxic conditions (95% O2/5% CO2) once or twice (12 slices in each group) before OGD

with 15-minute washout after each exposure. During OGD experiments

hippocampus slices were bathed with artificial cerebrospinal fluid (ACSF) lacking glucose and perfused with 95% N2 and 5% CO2 for 14 minutes

followed by a 30-minute reperfusion in normal ACSF. The CA1 population spike (PS) was measured and used to quantify the degree of neuronal function recovery after OGD. To assess the role of mitogen-activated protein kinases (MAPKs) in isoflurane preconditioning

U0126

an inhibitor of extracellular signal-regulated protein kinase (ERK1/2)

and SB203580

an inhibitor of p38 MAPK

were used before two periods of 3vol% isoflurane exposure. Results The degree of neuronal function recovery of hippocampal slices exposed to 1vol%

2vol%

or 3vol% isoflurane once was 41.88%±9.23%

55.05%±11.02%

or 63.18%±10.82% respectively. Moreover

neuronal function recovery of hippocampal slices exposed to 1vol%

2vol%

or 3vol% isoflurane twice was 53.75%±12.04%

63.50%±11.06%

or 76.25%±12.25%

respectively. Isoflurane preconditioning increased the neuronal function recovery in a dose-dependent manner. U0126 blocked the preconditioning induced by dual exposure to 3vol% isoflurane (6.13%±1.56%

P<0.01) and ERK1/2 activities. Conclusions Isoflurane is capable of inducing preconditioning in hippocampal slices in vitro in a dose-dependent manner

and dual exposure to isoflurane with a lower concentration is more effective in triggering preconditioning than a single exposure. Isoflurane-induced neuroprotection might be involved with ERK1/2 activities.