| Objective:To investigate the protective effects of 2.4% and 4.0% sevoflurane postconditioning against cerebral ischemia-reperfusion injury in rats. Methods:Adult male Sprague-Dawley rats (300-350g) were randomly assigned into four groups:Sham group, Ischemia reperfusion group (I/R), Ischemia-reperfusion+2.4% Sevoflurane group (Sevol), Ischemia reperfusion+4.0% Sevoflurane group (Sevo2). The left distal middle cerebral artery was occluded permanently by electrocogulation; subsequently both commom carotid arteries were exposed and occluded with miniature clips for 60 mins. Lossening the clips resulted in the cerebral ischemia-reperfusion injury. Tracheal intubated, at the same time of reperfusion, the animals were inhaled of 2.4% or 4% sevoflourane +oxygen or 100% oxygen for 60 mins. The Sham group was exposed the left distal middle cerebral artery and the commom carotid arteries, but did not operated. Physiological variables (mean arterial blood pressure, heart rate, temperature, plasma glucose and arterial blood gases)were measured 5 min after induction of anesthesia,15 min after ischemic,15 min after reperfusion. Results:Compared with Sham group, the mean arterial blood pressure was lower in Sevo2 group 15 min after reperfusion. No difference was found in rectal temperature, mean arterial blood pressure, arterial pH, PaCO2, PaO2 and blood glucose level in other groups. Compared with I/R group, the Sevol and Sevo2 groups improved the neurological functions and increased the numbers of the surviving nerve cells in ischemic penumbra after pMCAO followed by reperfusion on 1d, 3d and 7d (P<0.05). Animals in Sevol and Sevo2 groups developed smaller brain infarct volumes than I/R group after reperfusion on 3d (P<0.05). But No difference was found in neurological scores, the numbers of the surviving nerve cells and the infarct volumes between the Sevol and Sevo2 groups (P>0.05). Conclusion:Sevoflurane postconditioning could induce the neuroprotection against cerebral ischemia-reperfusion injury, but the protective effect was not dose-dependent in this model.Objective:To investigate the effects of sevoflurane on PI3K/Akt/ GSK-3βpathway and MPTP in this neuroprotection against cerebral ischemia reperfusion. Methods:Adult male Sprague-Dawley rats (300-350g) were randomly assigned into eight groups:Sham group, Ischemia-reperfusion group (I/R), Ischemia-reperfusion+Sevoflurane group (Sevo), Ischemia-reperfusion+DMSO group (DMSO), Ischemia reperfusion+Sevoflurane+a selective mitochondrial permeability transition pore (MPTP) opener Atractyloside group (Sevo+Atr), Ischemia reperfusion+Sevoflurane+a selective PI3K inhibitor LY294002 group (Sevo+LY), Ischemia reperfusion+Atractyloside group (Atr), Ischemia reperfusion+LY294002 group (LY). Atractyloside (1.6mg/mL,30μL, in DMSO) and LY294002 (1.7mg/mL,30μL, in DMSO) were right intracerebroventricularly injected before the reperfusion. Result:Compared with I/R group, sevoflurane inhibited the decrease of calcium induced mitochondrial absorbance at 520 nm (A520), improved neurological functions and developed smaller brain infarct volumes (P<0.05). This protection was reversed by administration of Atractyloside and LY294002, but no distinguished difference was found among I/R, DMSO, Atr and LY groups (P>0.05). Compared with I/R group, sevoflurane postconditioning could not only increase the phosphorylated Akt and GSK-3βin ischemic penumbra, but also inhibit the MPTP opening (P<0.05). This effect was also abolished by LY294002. Conclusion:The sevoflurane postconditioning induced neuroprotective effect could be exerted via the activation of the PI3K/Akt/GSK-3p pathway and inhibition of MPTP.Objective:To study the effects of sevoflurane on neuronal apoptosis, caspase-3,8,9 expressions after cerebral ischemia in rats, and to disclose the relationship between MPTP and neuronal apoptosis. Methods:Adult male Sprague-Dawley rats (300-350g) were randomly assigned into seven groups:Sham group, Ischemia-reperfusion group (I/R), Ischemia-reperfusion+Sevoflurane group (Sevo), Ischemia-reperfusion +Sevoflurane+a selective MPTP opener Atractyloside group (Sevo+Atr), Ischemia reperfusion+Sevoflurane+a selective PI3K inhibitor LY294002 group (Sevo+LY), Ischemia-reperfusion+ Atractyloside group (Atr), Ischemia-reperfusion+LY294002 group (LY).At the 1d,3d and 7d after reperfusion, the rats were anesthetized and the brains were removed. Caspase-3,8,9 expressions were determined by immunohistological staining. Apoptosis was also determined by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) staining. Result: Compared with I/R group, sevoflurane decreased the numbers of TUNEL and caspase-3,9 positive cells in ischemic penumbra (P<0.05). This effect was also abolished by Atractyloside and LY294002. No distinguished difference was found among I/R and Sevo groups about caspase-8. Conclusion:Sevoflurane postconditioning could inhibit the neuronal apoptosis by inactivating the mitochondrial pathway of apoptosis in cerebral ischemia reperfusion injury. The neuroprotection of sevoflurane may be mediated by PI3K/Akt pathway and MPTP.Objective:To investigate the effects of sevoflurane postconditioning on BDNF and VEGF in ischemic penumbra after cerebral ischemic reperfusion. Methods:Adult male Sprague-Dawley rats (300-350g) were randomly assigned into three groups:Sham group, Ischemia-reperfusion group (I/R), Ischemia-reperfusion+Sevoflurane group (Sevo). The expressions of BDNF and VEGF in ischemic penumbra were determined by RT-PCR and Western blot after reperfusion on 6h, 1d,3d and 7d. Result:Compared with Sham group, the expressions of BDNF and VEGF in I/R group were increased. Compared with I/R group, sevoflurane postconditioning could significantly increase the levels of BDNF and VEGF. Conclusion:Sevoflurane postconditioning could play a neuroprotective role by increasing the levels of BDNF and VEGF in penumbra after cerebral ischemic reperfusion.
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