PMID- 12105371 OWN - NLM STAT- MEDLINE DCOM- 20020806 LR - 20190727 IS - 1524-4628 (Electronic) IS - 0039-2499 (Linking) VI - 33 IP - 7 DP - 2002 Jul TI - Tolerance against ischemic neuronal injury can be induced by volatile anesthetics and is inducible NO synthase dependent. PG - 1889-98 AB - BACKGROUND AND PURPOSE: We tested whether volatile anesthetics induce neuroprotection that is maintained for a prolonged time. METHODS: Rats were pretreated for 3 hours with 1 minimal anesthetic concentration of isoflurane or halothane in normal air (anesthetic preconditioning [AP]). The animals were subjected to permanent middle cerebral artery occlusion (MCAO) at 0, 12, 24, or 48 hours after AP. Halothane-pretreated animals were subjected to MCAO 24 hours after AP. Histological evaluation of infarct volumes was performed 4 days after MCAO. Cerebral glucose utilization was measured 24 hours after AP with isoflurane. Primary cortical neuronal cultures were exposed to 1.4% isoflurane for 3 hours. Oxygen-glucose deprivation (OGD) was performed 24 hours after AP. Injury was assessed 24 hours later by measuring the release of lactate dehydrogenase into the medium 24 hours after OGD. RESULTS: Isoflurane anesthesia at 0, 12, and 24 hours before MCAO or halothane anesthesia 24 hours before MCAO significantly reduced infarct volumes (125+/-42 mm3, P=0.024; 118+/-51 mm3, P=0.008; 120+/-49 mm3, P=0.009; and 121+/-48 mm3, P=0.018, respectively) compared with control volumes (180+/-51 mm3). Three hours of isoflurane anesthesia in rats did not have any effect on local or mean cerebral glucose utilization measured 24 hours later. Western blot analysis from cortical extracts of AP-treated animals revealed an increase of the inducible NO synthase (iNOS) protein beginning 6 hours after AP. The iNOS inhibitor aminoguanidine (200 mg/kg IP) eliminated the infarct-sparing effect of AP. In cultured cortical neurons, isoflurane exposure 24 hours before OGD decreased the OGD-induced release of lactate dehydrogenase by 49% (P=0.002). CONCLUSIONS: Pretreatment with volatile anesthetics induces prolonged neuroprotection in vitro and in vivo, a process in which iNOS seems to be critically involved. FAU - Kapinya, Krisztian J AU - Kapinya KJ AD - Department of Experimental Neurology, Medical Faculty Charite, Humboldt-University, Berlin, Germany. FAU - Lowl, Diana AU - Lowl D FAU - Futterer, Carsten AU - Futterer C FAU - Maurer, Martin AU - Maurer M FAU - Waschke, Klaus F AU - Waschke KF FAU - Isaev, Nikolaj K AU - Isaev NK FAU - Dirnagl, Ulrich AU - Dirnagl U LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Stroke JT - Stroke JID - 0235266 RN - 0 (Anesthetics, Inhalation) RN - 0 (Enzyme Inhibitors) RN - 0 (Neuroprotective Agents) RN - CYS9AKD70P (Isoflurane) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, rat) RN - IY9XDZ35W2 (Glucose) RN - UQT9G45D1P (Halothane) SB - IM MH - Anesthetics, Inhalation/*pharmacology MH - Animals MH - Body Temperature/drug effects MH - Brain/blood supply/drug effects/metabolism/pathology MH - Brain Infarction/etiology/pathology/*prevention & control MH - Brain Ischemia/complications/*drug therapy MH - Cells, Cultured MH - Cerebral Infarction MH - Disease Models, Animal MH - Enzyme Inhibitors/pharmacology MH - Glucose/metabolism MH - Halothane/pharmacology MH - Infarction, Middle Cerebral Artery/complications/drug therapy/pathology MH - Isoflurane/pharmacology MH - L-Lactate Dehydrogenase/metabolism MH - Male MH - Neurons/cytology/*drug effects/pathology MH - Neuroprotective Agents/pharmacology MH - Nitric Oxide Synthase/antagonists & inhibitors/*metabolism MH - Nitric Oxide Synthase Type II MH - Rats MH - Rats, Wistar MH - Time Factors EDAT- 2002/07/10 10:00 MHDA- 2002/08/07 10:01 CRDT- 2002/07/10 10:00 PHST- 2002/07/10 10:00 [pubmed] PHST- 2002/08/07 10:01 [medline] PHST- 2002/07/10 10:00 [entrez] AID - 10.1161/01.str.0000020092.41820.58 [doi] PST - ppublish SO - Stroke. 2002 Jul;33(7):1889-98. doi: 10.1161/01.str.0000020092.41820.58.