We monitored survival of Purkinje cells in rat cerebellar slices to test the hypothesis that isoflurane preconditioning reduces ischemia-induced neuronal death. Preconditioning the brain slices with isoflurane, a volatile anesthetic commonly used in clinical practice, at 1-4% for 15 min at 37 degreesC significantly decreased Purkinje cell injury and death caused by a 20-min ischemia (simulated by oxygen-glucose deprivation, OGD). The effective concentration for half of the maximal effect (EC50) for this isoflurane preconditioning-induced neuroprotection was 1.17+/-0.31% and the maximal protective effects were achieved at 3% or higher concentrations of isoflurane. In addition, preconditioning the cells with isoflurane for 15-30 min was needed for the preconditioning to be maximally protective. Although farnesyl protein transferase inhibitor III blocked the protective effects of OGD preconditioning (a 3-min OGD 15 min before the 20-min OGD), this inhibitor did not affect the neuroprotection induced by isoflurane preconditioning. While (DL)-threo-beta-hydroxyaspartic acid (THA), a specific glutamate transporter inhibitor, did not change basal OGD-induced cell death rate, THA blocked the neuroprotection induced by isoflurane preconditioning but not by OGD preconditioning. Glybenclamide, a K-ATP channel inhibitor, did not block the neuroprotection induced by either isoflurane or OGD preconditioning. Our results suggest that isoflurane preconditioning is neuroprotective. The isoflurane concentrations and times needed for the preconditioning to be neuroprotective are clinically relevant. The mechanisms of this protection seem to involve modulation of glutamate transporter activity. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.
