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In this study, we aimed to assess the neuroprotective effect of sevoflurane preconditioning in a cerebral focal ischemia-reperfusion rat model. Sixty Sprague Dawley rats were divided into six groups: sham operated group, cerebral focal ischemia-reperfusion (CIR) group, CIR+sevoflurane preconditioning (SP) (2%) group, CIR+sevoflurane preconditioning (2.5%) group, CIR+sevoflurane preconditioning (3%) group, and CIR+sevoflurane preconditioning (3.5%) group. All subjects were euthanized 2days post-surgery and their hippocampus tissues were removed. Tissue malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) levels were measured and hippocampus tissue samples were examined histopathologically. Results showed that significant difference in antioxidant, immunity indexes, and apoptosis-related protein expression was detected in hippocampus tissue between sham-operated control and CIR groups. Sevoflurane preconditioning significantly dose-dependently reduced MDA, IL-1β, IL-6, IL-10 and TNF-α levels and enhanced antioxidant enzyme activities in hippocampus tissue of CIR+SP groups compared to CIR group. In addition, sevoflurane preconditioning significantly dose-dependently upregulated PI3K, p-Akt and Bcl-2 levels and downregulated caspase-3 and Bax levels in hippocampus tissue of CIR+SP groups compared to CIR group. It can be concluded that sevoflurane preconditioning demonstrates a strong and ameliorative effect on cerebral I/R damage in rats. The neuroprotective mechanisms of sevoflurane preconditioning are associated with its properties of anti-apoptosis and anti-oxidation as well as regulation of PI3K and p-Akt signal activation.

Tea polyphenols (TP) was investigated in rats for its protective effect on renal ischemia/reperfusion injury (RIRI). Rats were randomized into groups as follows: (I) sham group (n = 10); (II) RIRI group (n = 10); (III) RIRI + TP (100 mg/kg) group (n = 5); (IV) RIRI + TP (200 mg/kg) group (n = 5); (V) RIRI + TP+ Astragalus mongholicus aqueous extract (AMAE) (300 mg/kg + 100 mg/kg) group (n = 5). For the IRI + TP groups, rats were orally given with tea polyphenols (100, 200 and 300 mg/kg body weight) once daily 10 days before induction of ischemia, followed by renal IRI. For the sham group and RIRI group, rats were orally given with equal volume of saline once daily 10 days before induction of ischemia, followed by renal IRI. Results showed that tea polyphenol pretreatment significantly suppressed ROS level and MDA release. On the other hand, in rats subjected to ischemia–reperfusion, the activities of endogenous antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GSH-Px) showed recovery, whereas the levels of urea nitrogen and serum creatinine were reduced by administration of tea polyphenols orally for 10 days prior to ischemia–reperfusion. Moreover, tea polyphenol pretreatment significantly decreased TLR4 and NF-κB p65 protein expression levels in RIRI rats. At the same time, tea polyphenol pretreatment attenuated the increased level of serum IL-1β, IL-6, ICAM-1 and TNF-α, and enhanced IL-10 production in RIRI rats. Furthermore, tea polyphenol pretreatment significantly decreased renal epithelial tubular cell apoptosis induced by renal ischemia/reperfusion, alleviating renal ischemia/reperfusion injury. These results cumulatively indicate that tea polyphenol pretreatment could suppress the TLR4/NF-κB p65 signaling pathway, protecting renal tubular epithelial cells against ischemia/reperfusion-induced apoptosis, which implies that antioxidants may be a potential and effective agent for prevention of the ischemic/reperfusion injury through the suppression extrinsic apoptotic signal pathway induced by TLR4/NF-κB p65 signal pathway. Moreover, supplement of AMAE can increased renal protection effect of TP.

Tumor necrosis factor (TNF) and the TNF receptor (TNFR) superfamily play very important roles for cell death as well as normal immune regulation. Previous studies have strongly suggested that c-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in ischemic brain injury. The purpose of this investigation was to examine the protective effect of remifentanil preconditioning in cerebral ischemia/reperfusion injury (CIR) and its possible molecular mechanism. Results showed that Remifentanil pretreatment significantly decreased the CD4(+) and increased the CD8(+) in cerebral tissues. Additionally, CD4(+)/CD8(+) in CIR + Remifentanil group was markedly lower than that in CIR group. TNF-α and TNFR1 in CIR + Remifentanil group rats was found to be significant lower than that in CIR group rats. The expression levels of Cyt-c, caspase-3, caspase-9 and pJNK proteins in brain of CIR + Remifentanil group rats were found to significantly decreased compared to CIR group rats. In addition, decreased ROS level indirectly inhibit JNK activation and cell death in CIR rat receiving Remifentanil preconditioning. From current experiment results, at least two signal pathways involve into the process of Remifentanil preconditioning inhibiting cerebral damage induced by ischemia reperfusion. The inhibitory effects of Remifentanil preconditioning on the brain damage are achieved probably through blocking the activation of TNF-α/TNFR1, JNK signal transduction pathways, which implies that Remifentanil preconditioning may be a potential and effective way for prevention of the ischemic/reperfusion injury through the suppression extrinsic apoptotic signal pathway induced by TNF-α/TNFR1, JNK signal pathways. Taken together, this study indicated that regulation of the TNF-α/TNFR1 and JNK signal pathways may provide a new therapy for cerebral damage induced by ischemia and reperfusion.