Pretreatment with volatile anesthetics, but not with the nonimmobilizer 1,2-dichlorohexafluorocyclobutane, reduced cell injury in rat cerebellar slices after an in vitro simulated ischemia

A prior exposure to the volatile anesthetic isoflurane has been shown to induce neuroprotection in rats. This phenomenon is called preconditioning. We designed this study to determine whether the potency of volatile anesthetics in inducing neuropreconditioning is related to their potency to induce anesthesia. Cerebellar slices of adult male Sprague–Dawley rats were exposed to various concentrations of isoflurane, halothane, sevoflurane, desflurane or the nonimmobilizer 1,2-dichlorohexafluorocyclobutane for 15 min, followed by a 15-min drug-free period, and then were subjected to oxygen–glucose deprivation for 10 min at 37 °C. After a 5-h recovery at 37 °C, brain slices were used for quantification of cell injury by spectrophotometric measurement of formazan produced from 2,3,5-triphenyltetrazolium chloride. All four volatile anesthetics induced a concentration-dependent preconditioning effect. The EC50 for this effect induced by isoflurane, halothane, sevoflurane or desflurane was 221, 173, 184 and 929 μM, respectively. This EC50 was linearly correlated with the aqueous concentration of one minimum alveolar concentration. The volatile anesthetic preconditioning-induced neuroprotection was abolished by dl-threo-β-hydroxyaspartic acid, dl-threo-β-benzyloxyaspartate or dihydrokainate, glutamate transporter inhibitors. The volatile nonimmobilizer 1,2-dichlorohexafluorocyclobutane at any concentrations tested in the study did not induce a significant preconditioning effect. Isoflurane preconditioning did not change the oxygen–glucose deprivation-induced glutamate accumulation. These results suggest that the preconditioning-induced neuroprotection by volatile anesthetics is not agent-specific. Mechanisms that are involved in inducing anesthesia may contribute to the induction of preconditioning effect by volatile anesthetics. Modification of glutamate transporter activity may be one of such mechanisms to induce these protective effects.