Sevoflurane immediate preconditioning alters hypoxic membrane potential changes in rat hippocampal slices and improves recovery of CA1 pyramidal cells after hypoxia and global cerebral ischemia.
Pretreatment with anesthetics before but not during hypoxia or ischemia can improve neuronal recovery after the insult. Sevoflurane, a volatile anesthetic agent, improved neuronal recovery subsequent to 10 min of global cerebral ischemia when it was present for 1 h before the ischemia. The mean number of intact hippocampal cornus ammonis 1 (CA1) pyramidal neurons in rats subjected to cerebral ischemia without any pretreatment was 17+/-5 (neurons/mm+/-S.D.) 6 weeks after the ischemia; naïve, non-ischemic rats had 177+/-5 neurons/mm. Rats pretreated with either 2% or 4% sevoflurane had 112+/-57 or 150+/-15 CA1 pyramidal neurons/mm respectively (P<0.01) 6 weeks after global cerebral ischemia. In order to examine the mechanisms of protection we used hypoxia to generate energy deprivation. Intracellular recordings were made from CA1 pyramidal neurons in rat hippocampal slices; the recovery of resting and action potentials after hypoxia was used as an indicator of neuronal survival. Pretreatment with 4% sevoflurane for 15 min improved neuronal recovery 1 h after the hypoxia; 90% of the sevoflurane-pretreated neurons recovered while none (0%) of the untreated neurons recovered. Pretreatment with sevoflurane enhanced the hypoxic hyperpolarization(-6.4+/-0.6 vs. -3.3+/-0.3 mV) and reduced the final level of the hypoxic depolarization (-39+/-6 vs. -0.3+/-2 mV) during hypoxia. Chelerythrine (5 muM), a protein kinase C/protein kinase M inhibitor, blocked both the improved recovery (10%) and the electrophysiological changes with 4% sevoflurane preconditioning. Two percent sevoflurane for 15 min before hypoxia did not improve recovery (0% recovery both groups) and did not enhance the hypoxic hyperpolarization or reduce the final depolarization during hypoxia. However if 2% sevoflurane was present for 1 h before the hypoxia then there was significantly improved recovery, enhanced hypoxic hyperpolarization, and reduced final depolarization. Thus we conclude that sevoflurane preconditioning improves recovery in both in vivo and in vitro models of energy deprivation and that preconditioning enhances the hypoxic hyperpolarization and reduces the hypoxic depolarization. Anesthetic preconditioning may protect neurons from ischemia by altering the electrophysiological changes a neuron undergoes during energy deprivation.
Wang
J
J
Department of Anesthesiology, Box 6, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
Lei
B
B
Popp
S
S
Meng
F
F
Cottrell
J E
JE
Kass
I S
IS
D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D002245:Carbon Dioxide / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D006863:Hydrogen-Ion Concentration; D002534:Hypoxia, Brain / Q000503:physiopathology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D008738:Methyl Ethers / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane
D008738:Methyl Ethers; D002245:Carbon Dioxide; D000077149:Sevoflurane; D005947:Glucose; D010100:Oxygen