The Effect Of Sevoflurane On Learning And Memory Function In Neonatal Na(i|¨)ve Mice And The Underlying Molecular Mechanism

Purpose:To observe whether sevoflurane induced learning and memory disability is time-dependent.Methods:Healthy C57BL/6neonatal naive mice aged6days were enrolled. They were randomly assigned to four groups. One exposure to sevoflurane group and it’s own control group, three exposures to sevoflurane group and it’s own control group. Neonatal naive mice in one exposure to sevoflurane group only received3%sevoflurane in60%oxygen for2hours on the postnatal6th day and pups in control group received60%oxygen on the same day. Neonatal naive mice in three times exposures to sevoflurane group received3%sevoflurane in60%oxygen for2hours on the postnatal6th day,7th day, and8th day, respectively. Pups in control group received60%oxygen on the same days. On the postnatal31st day, Morris water maze was carried out to detect the learning and memory ability in mice.Results:Compared to it’s own control group, the swimming speed, escape latency, and times crossing the platform were not significantly different in one exposure to sevoflurane group (p>0.05). Compared to it’s own control group, swimming speed was comparable in three exposures to sevoflurane group (p>0.05). However, escape latency prolonged and times crossing the platform decreased in three exposures to sevoflurane group, the differences were statistically significant (p<0.05).Conclusion:Learning and memory function was not impaired after one exposure to sevoflurane in neonatal naive mice. But learning and memory function was impaired after three exposures to sevoflurane in neonatal naive mice. Purpose:To explore the underlying molecular mechanism of learning and memory disability after multiple sevoflurane exposure in neonatal mice.Methods:Healthy C57BL/6neonatal naive mice aged6days were enrolled. They were randomly assigned to four groups. One exposure to sevoflurane group and it’s own control group, three exposures to sevoflurane group and it’s own control group. Neonatal naive mice in one exposure to sevoflurane group only received3%sevoflurane in60%oxygen for2hours on the postnatal6th day and pups in control group received60%oxygen on the same day. Neonatal naive mice in three exposures to sevoflurane group received sevoflurane in60%oxygen for2hours on the postnatal6th day,7th day, and8th day, respectively. Pups in control group received60%oxygen on the same days. At the end of anesthesia, the mice were killed and the brains were harvested. The expression of caspase-3, inflammation mediators IL-1, IL-6, TNF-a, and protein Aβ in cortex were detected with Western Blot technique. The total number of TUNEL positive cells was counted in hippocampus.Results:Compared to it’s own control group, the activation of caspase-3was a little bit high in one exposure to sevoflurane group, the difference was not significant (p>0.05). Compared to it’s own group, three sevoflurane anesthesia caused extensive neuroapoptosis in neonatal mice including higher expression of caspase-3in cortex and more TUNEL positive cells in hippocampus. The difference was statistically significant (p<0.05). Inflammation mediators IL-1, IL-6, and TNF-α were higher in three exposures to sevoflurane group, and protein Aβ was higher in three exposures to sevoflurane group, The differences were statistically significant (p<0.05).Conclusion:One exposure to sevoflurane did not cause extensive neuro-apoptosis in neonatal naive mice. Three times sevoflurane anesthesia caused more extensive brain cell apoptosis in central nervous system, higher expression of inflammation mediator and protein Aβ in cortex which may lead to learning and memory dysfunction in neonatal mice. Purpose:To observe the potential effect of enriched environment on attenuating multiple anesthesia-induced learning and memory disability in neonatal mice.Methods:Healthy C57BL/6neonatal naive mice aged6days were enrolled. They were randomly assigned to two groups. Three exposures to sevoflurane followed by enriched environment group and control group. Neonatal naive mice in three exposures to sevoflurane followed by enriched environment group received3%sevoflurane in60%oxygen for2hours on the postnatal6th day,7th day, and8th day, respectively. Neonatal naive mice in control group received60%oxygen on the same days. From the9th day to the30th day, pups in both groups lived in an enriched environment for2hours a day. On31st day, Morris water maze was applied to detect learning and memory ability in mice.Results:Compared to control group, the swimming speed, escape latency, and times passing cross the platform were comparable, the difference were not statistically significant (P>0.05).Conclusion:Enriched environment plays a role in attenuating sevoflurane-induced learning and memory disability.