Effects of pioglitazone on cognitive impairments induced by isoflurane anesthesia in aged mice

AIM：To investigate the effects of pioglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) agonist, on the cognitive impairments and inflammatory cytokine production induced by isoflurane in aged mice. METHODS：Male C57BL/6J mice (11-month-old, n=136) were assigned randomly into 5 groups: control group (Con), isoflurane group (Iso), 10 mg/kg pioglitazone + isoflurane group (Pi10+Iso), 20 mg/kg pioglitazone + isoflurane group (Pi20+Iso) and 20 mg/kg pioglitazone alone group (Pi20). The mice in all isoflurane-treated groups were exposed to oxygen mixed with 1.4% isoflurane for 2 h. The mice in Con group and in Pi20 group were exposed to oxygen only for 2 h. Pioglitazone was suspended in 1% carboxymethyl cellulose (CMC). Pioglitazone (10 mg/kg or 20 mg/kg) was gavaged 2 h prior to the exposure of isoflurane or oxygen alone. The same volume of 1% CMC was gavaged in Con group and in Iso group. Fear conditioning tests were performed to determine the learning and memory abilities 48 h after isoflurane exposure. Fresh cerebral cortice and hippocampi were dissected to measure the protein expression of PPARγ by Western blotting, and the contents of IL-1β and TNF-α were analyzed by ELISA 6 h after isoflurane exposure. RESULTS：Compared with Con group, the response of freezing behavior decreased (P<0.05) and IL-1β content in the hippocampus increased (P<0.05) in Iso group. Compared with Iso group, the response of freezing behavior and PPARγ protein expression level had no significant change (P>0.05) in Pi10+Iso group, but the response of freezing behavior and PPARγ protein expression level increased significantly (P<0.05) and IL-1β content in the hippocampus decreased (P<0.05) in Pi20+Iso group. IL-1β content in the cerebral cortex and TNF-α levels both in the cerebral cortex and the hippocampus showed no significant difference among all groups (P>0.05). CONCLUSION：Pioglitazone attenuates cognitive impairments and the elevates the level of IL-1β in the hippocampus induced by isoflurane in aged mice.