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.