Abstract

Inhalation anesthetics are reported to affect cognition in both animals and humans. The influence of inhalation anesthetics in learning and memory are contradictory. We therefore investigated the effects of sevoflurane anesthesia with different durations on cognitive performance and the levels of NMDA receptor subunit NR2B, phosphorylated ERK1/2 (p-ERK1/2) and activated caspase3 in mouse hippocampus. We anaesthetized eight-week old male C57BL/6 mice with 2.5% sevoflurane for durations ranging from one to four hours. Non-anaesthetized mice served as controls. Mice exposed to sevoflurane for one to three hours showed improved performance, whereas mice with exposure up to four hours displayed similar behavioral performance as control group. NR2B was increased both at 24h and at two weeks post sevoflurane exposure in all groups. The p-ERK1/2: total ERK1/2 ratio increased at 24h in all anesthesia groups. The ratio remained elevated at two weeks in groups with two- to four-hour exposure. Activated caspase3 was detected elevated at 24h in groups with two- to four-hour exposure. The elevated trend of activated caspase3 was still detectable at two weeks in groups with three- to four-hour exposure. At two weeks post anesthesia, the typical morphology associated with apoptotic cells was observed in the hippocampus of mice exposed to four hours of sevoflurane. Our results indicate that 2.5% sevoflurane exposure for one to three hours improved spatial cognitive performance in young adult mice. The cognitive improvement might be related to the increase of NR2B, the p-ERK1/2: total ERK1/2 ratio in hippocampus. However, exposure to sevoflurane for four hours caused neurotoxicity due to caspase3 activation and apoptosis.

Highlights

  • Animal and human studies proved that inhalation anesthetics affect cognitive function[1,2,3,4,5,6]

  • No significant differences in swimming speed were noticed between anesthetic groups and control group

  • We evaluated the levels of NR2B subunit and Extracellular signal-regulated kinase 1 and 2 (ERK1/2) in mouse hippocampus as the expression of NR2B and ERK1/2 in hippocampus was closely related with hippocampus-dependent spatial learning and memory tasks[21]

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Summary

Introduction

Animal and human studies proved that inhalation anesthetics affect cognitive function[1,2,3,4,5,6]. Their short term effects as amnesic agents are well known, while their long term effects, and especially their pro-cognitive effects need to be better presented. Several studies reported sevoflurane neurotoxicity and cognitive impairment focused on neonatal mice [10,11,12]. While the effects of sevoflurane on adult mice cognition are fewer reported. It is recently reported that sevoflurane anesthesia induced even an improvement of adult mice cognitive performance 24 hours after anesthesia[13]. We still have no information about how long these effects last and how they have been interpreted

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