Dual Isoflurane-induced Preconditioning Improves Neuroprotection in Rat Brain In Vitro and the Role of Extracellular Signal-regulated Protein Kinase

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.