Summary： This study investigated the role of glycogen synthase kinase-3D （GSK-3β） in isoflu- rane-induced neuroinflammation and cognitive dysfunction in aged rats. The hippocampi were dissected from aged rats which had been intraperitoneally administered lithium chloride （LiC1, 100 mg/kg） and then exposed to 1.4% isoflurane for 6 h. The expression of GSK-313 was detected by Western blotting. The mRNA and protein expression levels of tumor necrosis factor （TNF）-a, interleukin （IL）-lβ and IL-6 were measured by real-time PCR and enzyme-linked immunosorbent assay （ELISA）, respectively. Mor- ris water maze was employed to detect spatial memory ability of rats. The results revealed that the level of GSK-3β was upregulated after isofurane exposure. Real-time PCR analysis demonstrated that isoflu- rane anesthesia increased mRNA levels of TNF-a IL-Iβ and IL-6, which was consistent with the ELISA results. However, these changes were reversed by prophylactic LiC1, a non-selective inhibitor of GSK-3β. Additionally, we discovered that LiC1 alleviated isoflurane-induced cognitive impairment in aged rats. Furthermore, the role of GSK-313 in isoflurae-induced neuroinflammation and cognitive dysfunction was associated with acetylation of NF-r,B p65 （Lys310）. In conclusion, these results suggested that GSK-3β is associated with isoflurane-induced upregulation of proinflammatory cytokines and cognitive disorder in aged rats.
