| Ischemic cerebral injury is a common complication during perioperative period. We found that ischemic preconditioning and various non-ischemic preconditioning (e.g. inhalation anesthetics, electric acupuncture and hyperbaric oxygen) could significantly attenuate ischemic cerebral injury. In 2003, Zhao et al. reported that repetitive cycles of briefly interrupted reperfusion/ischemia applied at the onset of coronary reflow significantly reduced ischemic myocardial injury, termed as"Ischemic Postconditioning"(IPost). Recently, we found the similar phenomena in ischemic cerebral and spinal injury. With significant advantages over ischemic preconditioning and a strong feasibility, IPost possesses a prosperous future in clinical application. However, IPost still has some limitations. So it is of great importance to search for the non-ischemic postconditioning methods that can mimic the protection of IPost. Sevoflurane, a new inhalation anesthetic, is now widely used in clinic. However, whether sevoflurane postconditioning (sevo-Post) can mimic ischemic postconditioning is unknown.In this study, using the Middle Cerebral Artery Occlusion model (MCAO) in rats, we investigated whether sevo-Post has a neuroprotective effect, and then studied the role of mPTP in sevo-Post. This study was divided into two parts. In Experiment one, the neuroprotection of sevo-Post on focal cerebral ischemia reperfusion injury and its dose-effect relationship were investigated. In Experiment two, the role of mPTP in the neuroprotection induced by sevo-Post was studied.Experiment One. The neuroprotection of sevoflurane postconditioning in focal cerebral ischemiaObjective To investigate the neuroprotective effect of sevoflurane postconditioning with different concentrations in focal cerebral ischemia when sevoflurane postconditioning was given at the onset of reperfusion and its dose-response. Methods Fifty male SD rats were randomly assigned to five groups (n=10 each): control group (con), oxygen group (O2) and 0.5MAC (sevo1), 1.0MAC (sevo2), 1.5MAC (sevo3) sevoflurane postconditioning groups. All animals were subjected to the right middle cerebral artery occlusion (MCAO) for 120min followed by reperfusion for 72h. The animals in sevo1, sevo2 and sevo3 groups were given 0.5, 1.0 and 1.5MAC sevoflurane inhalation from 20min before to 10min after reperfusion. The neurological behaviour scores (NBS) were recorded at 24h, 48h, and 72h after reperfusion. Infarct volume percentage was determined after the last NBS assessment. Results The infarct volume percentage ratio of sevo1, sevo2 and sevo3 groups were 0.39±0.03, 0.31±0.03 and 0.24±0.03, respectively (P<0.05 among the groups), which were significantly smaller than con group (0.53±0.05, P<0.05). The infarct volume percentage of O2 group was 0.51±0.05, which was not significantly different from that of con group (P>0.05). NBS of 24h, 48h and 72h after reperfusion in all sevoflurane groups were significantly higher than those in con and O2 groups. Conclusion 0.5, 1.0 and 1.5MAC sevoflurane postconditioning had significant neuroprotective effect and this effect was dose-dependent.Experiment Two. The effect of mPTP on the neuroprotection induced by sevo-Postconditoning in focal cerebral ischemiaPart One The effect of Atractyloside (Atr) on sevoflurane postconditioning in focal cerebral ischemiaObjective To investigate the effect of Atractyloside on sevoflurane postconditioning in focal cerebral ischemia. Methods Fifty male SD rats were randomly assigned to five groups (n=10 each): con group (con), 1.0MAC group (Sevo), 1.0MAC+Atractyloside group (Sevo+Atr), 1.0MAC+vehicle group (Sevo+vehicle) and Atractyloside group (Atr). The animals in Sevo groups were given 1.0MAC sevoflurane inhalation from 20min before to 10min after reperfusion. The animals in Atr groups were given Atractyloside by ICV (Intracerebroventricular injection, ICV) injection before sevoflurane postcondioning. The NBS were recorded at 24h, 48h, and 72h after reperfusion. Infarct volume percentage was determined after the last NBS assessment. Results The infarct volume percentage ratio of sevo group (0.32±0.05) was significantly smaller than that of con group (0.53±0.07, P<0.05). The infarct volume percentage of Sevo +Atr group was 0.57±0.06, which was not significantly different from that of con group (P>0.05). The infarct volume percentage of Sevo+vehicle group (0.35±0.06) was not significantly different from that of Sevo group (P>0.05). NBS of 24h, 48h and 72h after reperfusion in Sevo group and Sevo+vehicle were significantly higher than that in con group. NBS of 24h, 48h and 72h after reperfusion in Sevo+Atr and Atr groups were significantly lower than that in con group. Conclusion Atractyloside abolished the neuroprotective effect of sevoflurane postconditioning on focal cerebral ischemia.Part Two The effect of Ciclosporin A on sevoflurane postconditioning in focal cerebral ischemiaObjective To investigate the effect of Ciclosporin A on sevoflurane postconditioning in focal cerebral ischemia. Methods Fifty male SD rats were randomly assigned to five groups (n=10 each): con group (con), 1.0MAC group (Sevo), 1.0MAC+ Ciclosporin A group (Sevo+CsA), 1.0MAC+ vehicle group (Sevo+vehicle) and Ciclosporin A group (CsA). The animals in Sevo groups were given 1.0MAC sevoflurane inhalation from 20min before to 10min after reperfusion. The animals in CsA groups were given Ciclosporin A by ICV injection before sevoflurane postcondioning. The NBS were recorded at 24h, 48h, and 72h after reperfusion. Infarct volume percentage was determined after the last NBS assessment. Results The infarct volume percentage ratio of Sevo, Sevo+CsA, CsA and Sevo+vehicle groups were 0.31±0.04, 0.25±0.04, 0.30±0.03 and 0.33±0.05, respectively (P<0.05 among the groups), which were significantly smaller than con group (0.55±0.05, P<0.05). The infarct volume percentage of Sevo+CsA group was 0.25±0.04, which was significantly different from that of Sevo group and that of CsA group (P<0.05). NBS of 24h, 48h and 72h after reperfusion in Sevo, Sevo+CsA, CsA and Sevo+vehicle groups were significantly higher than that in con group. Conclusion Both Ciclosporin A and 1.0MAC sevoflurane postconditioning had significant neuroprotective effects on focal cerebral ischemia/reperfusion injury. The combined neuroprotection was superior to each alone.Conclusion1. 0.5, 1.0 and 1.5MAC sevoflurane postconditioning had significant neuroprotective effect in focal cerebral ischemia and this neuroprotective effect was dose-dependent.2. Mitochondrial Permeability Transition Pore played an important role in the neuroprotective effect of sevoflurane postconditioning in focal cerebral ischemia.
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