title: Suppression of inflammatory response by flurbiprofen following focal cerebral ischemia involves the NF-κB signaling pathway.
abstract: Some studies of animal models of middle cerebral artery occlusion indicate that inflammation plays a key role in the pathogenesis of cerebral ischemia and secondary damage. Flurbiprofen has been suggested to alleviate cerebral ischemia/reperfusion injury in both focal and global cerebral ischemia models, but the mechanisms underlying the protective action are still incompletely understood. In this study we want to investigate the protective effect of flurbiprofen after transient middle cerebral artery occlusion (MCAO) in rats and the role of the NF-κB signaling pathway on this neuroprotective effect. Male Wistar rats were subjected to transient middle cerebral artery occlusion for 2 h, followed by 24 h reperfusion. Flurbiprofen was administrated via tail-vein injection at the onset of reperfusion. HE staining and Immunohistochemistry were carried out to detect the morphological changes in ischemic penumbra cortex. The expression of inflammatory cytokines genes (IL-1β, IL-6 and TNF-α) and the levels of p-NF-κB (p65) in ischemic penumbra cortex were measured by RT-PCR and western blot. Administration of flurbiprofen at the doses of 5 mg/kg and 10 mg/kg significantly attenuated cerebral ischemia/reperfusion injury, as shown by a reduction in the morphological changes and inhibition of pro-inflammatory cytokine expression in ischemic penumbra cortex. Moreover, our findings further demonstrated that the inhibition of NF-κB activity was involved in the neuroprotective effect of flurbiprofen on inflammatory responses. Flurbiprofen protects against cerebral injury by reducing expression of inflammatory cytokines genes and this effect may be partly due to the inhibition of NF-κB signaling pathway.
authors.affiliation: Departments of Anesthesiology, Qilu Hospital, Shandong University Jinan, China.
authors.forename: Bao-Zhu
authors.initials: BZ
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine Jinan, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Departments of Anesthesiology, Qilu Hospital, Shandong University Jinan, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Departments of Anesthesiology, Qilu Hospital, Shandong University Jinan, China.
authors.forename: Huan-Liang
authors.initials: HL
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine Jinan, China.
authors.forename: Xin-Bing
authors.initials: XB
authors.lastname: Wei
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine Jinan, China.
authors.forename: Yan-Xiao
authors.initials: YX
authors.lastname: Xiang
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine Jinan, China.
authors.forename: Xiu-Mei
authors.initials: XM
authors.lastname: Zhang
keywords: Flurbiprofen; focal cerebral ischemia; inflammation; nuclear factor-κB