title: Dual isoflurane-induced preconditioning improves neuroprotection in rat brain in vitro and the role of extracellular signal--regulated protein kinase.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Shihezi Medical School , Shihezi University , Shihezi 832008, China. iamsheng2006@163.com
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
authors.forename: Su-xiang
authors.initials: SX
authors.lastname: Guo
authors.forename: Zhi-gang
authors.initials: ZG
authors.lastname: Dai
authors.forename: Xi-wei
authors.initials: XW
authors.lastname: Dong
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Shan
authors.initials: S
authors.lastname: Jiang
authors.forename: Zhi-ping
authors.initials: ZP
authors.lastname: Wang
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology*; D019194:Ischemic Preconditioning; D007530:Isoflurane / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D007530:Isoflurane; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases