Remifentanil preconditioning alleviating brain damage of cerebral ischemia reperfusion rats by regulating the JNK signal pathway and TNF-α/TNFR1 signal pathway

Abstract

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.

Effects of remifentanil with or without midazolam pretreatment on the 95% effective dose of propofol for loss of consciousness during induction

“…The optimal dosage of remifentanil pretreatment can offer hemodynamic stability during maneuvers in the induction period, including laryngoscopy and intubation, [ 9 , 10 ] and it was also shown to have protective effects on organs in animal studies. [ 13 – 15 ] In addition, it is reported that remifentanil pretreatment can prevent pain caused by propofol injection. A few studies used target-controlled infusion to investigate the hypnotic dose of propofol when combined with remifentanil and the effects of combined treatment on hemodynamics.…”

Remifentanil Ameliorates Liver Ischemia-Reperfusion Injury Through Inhibition of Interleukin-18 Signaling

“…It has gained increasing attention as an opioid because several studies reported that it can protect myocardium and cerebrum against I/R injury. 13,14 However, the effects and mechanisms of remifentanil on liver I/R injury remain unknown. Previous studies have reported that remifentanil and other opioids can modulate the activities of several transcription factors, including NF-κB, signal transducer and activator of transcription 1 and CCAAT/ enhancer-binding protein β.…”

Treatment of surgical brain injury by immune tolerance induced by intrathymic and hepatic portal vein injection of brain antigens

“…Moreover, the CD4 + T/CD8 + T ratio was notably decreased upon drug intervention27. Another study also demonstrated that the CD4 + T/CD8 + T cell ratio increased in cerebral ischemia/reperfusion injury sites28. In experimental stroke, CD4 + T lymphocytes and CD8 + T lymphocytes contribute to inflammation, brain injury, and neurological deficit.…”