title: Isoflurane preconditioning reduces purkinje cell death in an in vitro model of rat cerebellar ischemia.
abstract: 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 degrees C 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 (EC(50)) 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.
authors.affiliation: Department of Anesthesiology, University of Virginia Health System, One Hospital Drive, P.O. Box 800710, Charlottesville, VA 22908-0710, USA.
authors.forename: S
authors.initials: S
authors.lastname: Zheng
authors.forename: Z
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002526:Cerebellar Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005905:Glyburide / Q000494:pharmacology; D019194:Ischemic Preconditioning / Q000379:methods*; D007530:Isoflurane / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D009924:Organ Culture Techniques; D063065:Organophosphonates / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C436083:2-(2-oxo-2-((3,7,11-trimethyl-2,6,10-dodecatrienyl)oxy)aminoethyl)phosphonic acid, (2,2-dimethyl-1-oxopropoxy)methyl ester sodium; D027322:Amino Acid Transport System X-AG; D018685:Anesthetics, Inhalation; D063065:Organophosphonates; D026902:Potassium Channel Blockers; C011274:3-hydroxyaspartic acid; D001224:Aspartic Acid; D007530:Isoflurane; D005905:Glyburide