Mechanism of Sevoflurane-induced Cognitive Impairment in Neonatal Mice
Objective To investigate the mechanism of Sevoflurane-induced postoperative cognitive dysfunction(POCD)in neonatal mice.Methods Twelve neonatal mice were randomly divided into Sevoflurane group and control group,with 6 cases in each group.The control group was given 60%oxygen inhalation,and the Sevoflurane group was given 3%Sevoflurane(large dose)plus 60%oxygen.The two groups were inhaled for 2 h a day for 3 days.The Morris water maze test was used to detect the cognitive and memory ability of mice.After the experiment,the cerebral cortex and hippocampal tissues of newborn mice were dissected,and pathological sections,HE,Nissl staining,TUNEL and transmission electron microscopy were performed to observe the morphological changes in the cerebral cortex and hippocampal tissues.Western blot and flow cy-tometry were used to detect apoptosis rate and protein expression of programmed necrosis in hippocampus.Results Compared with the control group,the escape latency of Sevoflurane group was significantly prolonged,the number of platform crossing was reduced,and the target quadrant residence time was shortened(P<0.01).HE staining showed that the degree of neuro-nal atrophy and cortical interstitial edema in Sevoflurane group was stronger than that in control group.The results of Nissl staining showed that the neuronal atrophy and nucleolysis were increased in Sevoflurane group compared with the control group,and the number of atrophic and degenerated cells in cerebral cortex and hippocampus tissue as well as the number of atrophic cells in the two groups was lower than that in the control group(P<0.01).The results of transmission electron mi-croscopy showed that the brain cells in Sevoflurane group were more damaged than those in control group.Compared with the control group,the relative expression levels of GRP78 and GRP94 proteins and the relative expression levels of P22,P47,Caspase-1,Caspase-3 and Caspase-9 proteins in hippocampal tissue of neonatal mice in Sevoflurane group as well as apoptosis rate were increased(P<0.01).Conclusion Large doses of Sevoflurane can induce endoplasmic reticulum stress in hipp-ocampal tissue of POCD neonatal mice,and then induce programmed necrosis of hippocampal tissue to aggravate the disease.
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