Isoflurane preconditioning and postconditioning in rat hippocampal neurons.
The volatile anesthetic isoflurane is capable of inducing preconditioning and postconditioning effects in the brain. However, the mechanisms for these neuroprotective effects are not fully understood. Here, we showed that rat hippocampal neuronal cultures exposed to 2% isoflurane for 30min at 24h before a 1h oxygen-glucose deprivation (OGD) and a 24h simulated reperfusion had a reduced lactate dehydrogenase release. Similarly, this OGD and simulated reperfusion-induced lactate dehydrogenase release was attenuated by exposing the neuronal cultures to 2% isoflurane for 1h at various times after the onset of the simulated reperfusion (isoflurane postconditioning). The combination of isoflurane preconditioning and postconditioning induced a better neuroprotection than either alone. Inhibition of the calcium/calmodulin-dependent protein kinase II (CaMKII), inhibition of N-methyl d-aspartate (NMDA) receptors, or activation of adenosine A2A receptors resulted in reduction of the OGD and simulated reperfusion-induced cell injury. The combination of CaMKII inhibition and isoflurane preconditioning or postconditioning did not provide better protection than CaMKII inhibition, isoflurane preconditioning, or isoflurane postconditioning alone. The combination of NMDA receptor inhibition and isoflurane postconditioning was not better than NMDA receptor inhibition or isoflurane postconditioning alone for neuroprotection. However, the combination of adenosine A2A receptor activation with either isoflurane preconditioning or isoflurane postconditioning induced a better neuroprotective effect than adenosine A2A receptor activation, isoflurane preconditioning, or isoflurane postconditioning alone. The combination of NMDA receptor inhibition and isoflurane preconditioning caused a better neuroprotective effect than NMDA receptor inhibition or isoflurane preconditioning alone. These results suggest that isoflurane preconditioning- and postconditioning-induced neuroprotection can be additive. Isoflurane preconditioning and isoflurane postconditioning may involve CaMKII inhibition, but may not involve adenosine A2A receptor activation. Inhibition of NMDA receptors may mediate the effects of isoflurane postconditioning, but not isoflurane preconditioning.
McMurtrey
Richard J
RJ
Department of Anesthesiology, University of Virginia, Charlottesville, VA 22908, USA.
Zuo
Zhiyi
Z
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000166:cytology*; D000860:Hypoxia; D007530:Isoflurane / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D007530:Isoflurane; D007770:L-Lactate Dehydrogenase; D005947:Glucose