Background: Isoflurane decreases ischemia-induced neuronal injury. The mechanisms of this effect are largely unknown. We hypothesize that isoflurane induces expression of protective stress genes and decreases expression of apoptosis-related genes.
Methods: The mRNA expression of about 1300 genes related to neurobiology in rat glial-neuronal cocultures was evaluated by microarray technology. Four experimental conditions were examined: control; 2% isoflurane; oxygen-glucose deprivation (OGD, to simulate ischemia in vitro); or isoflurane (2%) plus OGD.
Results: There were four immediate early genes/transcription factors (early growth response 1, c-fos, nerve growth factor-induced factor A and Knox-24) whose mRNA expression was increased to more than 1.4-fold of control levels under the conditions of isoflurane, OGD or isoflurane plus OGD. Isoflurane increased the mRNA expression of heme oxygenase, a 32-kDa heat-shock protein, and decreased the mRNA expression of caspase-2, calpain 1 and the Bcl-2-associated death agonist. These isoflurane effects were still apparent under the condition of isoflurane plus OGD. The mRNA expression of Gbeta1, early growth response 1 and the death effector domain-containing protein DEFT in the samples used for microarray assay was determined by reverse transcriptase-polymerase chain reaction, and the results were consistent with the patterns of changes across the experimental conditions as revealed by microarray technology.
Conclusion: Our data suggest that the effects of isoflurane on the mRNA expression of multiple genes in glial-neuronal cocultures are consistent with its neuroprotection against ischemia. A coordinated change in expression of many genes (increased expression of potentially protective gene and decreased expression of potentially damaging genes) after the exposure of isoflurane was revealed by this study.