Sex-specific effects of sevoflurane on cognitive function of postnatal rats

Objective　To investigate the gender difference of cognitive function in neonatal rats treated with sevoflurane. Methods　Eighty two postnatal 7-day (P7) SD rats were randomly divided into control group and sevoflurane treated group, then divided into the following subgroups according to gender: female control group, male control group, female sevoflurane treated group, and male sevoflurane treated group. After inhaling air or 4% sevoflurane for 4 hours, the levels of serum cortisone and estradiol (E2) were detected by ELISA, and the expressions of Ki-67 and neuronal core antigen (NeuN) in hippocampus were detected by immunohistochemistry. The open field experiment was performed with rat P21 and Morris water maze experiment was performed with rat P35 to explore the effects of sevoflurane exposure on the spatial cognitive function in different gender of rats. Results　ELISA reveled that, compared with the control group, the serum cortisone level in sevoflurane treated group was significantly higher [(11.60±1.41) ng/ml vs. (7.93±1.58) ng/ml, P 0.05]; and no significant difference existed in the levels of cortisone and E2 between different genders (P>0.05). Immunohistochemistry showed that the number of Ki-67 and NeuN positive cells in hippocampal CA1 and dentate gyrus (DG) decreased significantly in sevoflurane treated group than those in control group (P 0.05). Morris water maze test showed that no significant difference was found among female rats (P>0.05); compared with male control group, the platform latency and moving distance of male sevoflurane treated group were significantly prolonged at the forth and fifth day of acquired training (P<0.01 or P<0.05). At the second day of counterpoint training, the platform latency and movement distance of rats in male sevoflurane treated group were significantly prolonged (P<0.05). In counterpoint exploration training, the platform latency of rats in male sevoflurane treated group was significantly prolonged (P<0.01), and the time spent in the target quadrant reduced significantly (P=0.031). Conclusions　Sevoflurane treatment has a great influence on the serum cortisone level of postnatal rats, may inhibit the proliferation of hippocampal neural stem cells and neurogenesis. The learning ability of male rats decreased after adulthood, but no obvious effect on female rats. DOI: 10.11855/j.issn.0577-7402.2021.02.02