The Dual Neuroprotective-Neurotoxic Effects of Sevoflurane After Hemorrhagic Shock Injury

Abstract

BackgroundThe neuroprotection and neurotoxicity induced by sevoflurane have been gradually established. Choosing anesthetic agents after hemorrhage shock and resuscitation (HSR) induced by bleeding can be challenging. We determined the dual neuroprotective-neurotoxic effects of sevoflurane postconditioning after HSR injury using a model of blood loss and reinfusion in rats via the heme oxygenase-1 (HO-1)/reactive oxygen species (ROS) signal pathway. MethodsThe rats were exposed to 2%-4% sevoflurane postconditioning in vivo after HSR. Learning ability was assessed 30 d after HSR by Morris water maze tests. Hippocampal apoptosis was assessed 7 d after HSR by TdT-mediated dUTP nick-end labeling combined with cleaved caspase-3 (17 kDa). The ROS, mitochondrial membrane potential (MMP), HO-1 expression, and HO activity 1 d after HSR were assessed by fluorometric, JC-1, Western blot, and bilirubin assays, respectively. ResultsCompared with HSR alone, 2% sevoflurane postconditioning improved latency and increased MMP levels, HO-1 expression, and HO activity but decreased TdT-mediated dUTP nick-end labeling-positive cells, cleaved caspase-3 (17 kDa) expression, and ROS production. Pretreatment with hemin, an HO-1 agonist, reversed these effects. Compared with 2% sevoflurane postconditioning plus HSR, slower latency; decreased MMP levels; and increased TdT-mediated dUTP nick-end labeling-positive cells, cleaved caspase-3 (17 kDa), HO-1 expression, HO activity, and ROS production were shown in HSR plus 4% sevoflurane postconditioning, whereas Tin-mesoporphyrin, an HO-1 inhibitor, partially reversed the neurodegeneration of 4% sevoflurane postconditioning. ConclusionThe dual neuroprotective-neurotoxic effects of 2%-4% sevoflurane postconditioning after HSR injury might be associated with increased ROS via the “threshold effect” of HO-1.