AbstractObjective To investigate the influence of isoflurane on cognitive function and the inhibitory effect of ERK phosphorylation on cognitive impairment induced by isoflurane in mice. Methods Sixty-six two-month-old C57BL/6J male mice were randomly divided into three groups: the control group (Con), isoflurane group (Iso), and Iso+U0126 group (IsoU). Mice in the Iso group and Iso + U0126 group were anesthetized by 1.4% isoflurane + 60% oxygen + 38.6% air for 2 hours, while those in the Con group inhaled 60% oxygen + 40% air alone for 2 hours. U0126 (100 mg/kg) was injected intraperitoneally into mice in the Iso+U0126 group before isoflurane treatment. After modeling, ELISA was used to detect the level of Aβ1-42 in the cortex of mice in each group. Western blot and immunofluorescence were used to determine the level of ERK1 phosphorylation in the cortex of these mice. The Morris water maze was used to detect the cognitive function of mice at day 1 to 7 after modeling. Results Compared with the Con group, the expression of p-ERK1 in the Iso group was up-regulated (0.35±0.02 vs. 0.17±0.03, P<0.05), so was the expression of Aβ1-42 (66.5±4.2 vs. 43.7±5.1, P<0.05), the escape latency was significantly prolonged (37.20±2.87 vs. 11.20±2.76), and the number of times the mice crossed the platforms was significantly reduced (2.80±1.48 vs. 5.60±1.96). Compared with the Iso group, the expression of p-ERK1 in the Iso+U0126 group was down-regulated (0.25±0.05 vs. 0.35±0.02, P<0.05), the escape latency was significantly shortened (15.30±4.76 vs. 37.20±2.87), and the number of times the mice crossed the platforms was significantly increased (5.30±2.58 vs. 2.80±1.48, P<0.05). Conclusions Two consecutive hours of exposure to 1.4% isoflurane can cause cognitive impairment in mice, and the inhibition by ERK phosphorylation can ameliorate cognitive impairment induced by isoflurane.
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