Abstract
ObjectiveThis study explored the effects of sevoflurane exposure during different stages of pregnancy on the brain development of offspring.MethodsThirty-six pregnant SD rats were randomly divided into 4 groups: control, sevoflurane exposure in early (S1) pregnancy, sevoflurane exposure in middle (S2) pregnancy, and sevoflurane exposure in late (S3) pregnancy. After natural birth, the learning and memory capacity of offspring rats was analyzed using the Morris water maze experiment. The hippocampi of offspring rats were collected. The levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the hippocampus were measured by ELISA. Additionally, the Nissl bodies in the hippocampus were analyzed using Nissl staining. Immunohistochemistry was used to examine the expression of BDNF and CPEB2 in the hippocampus of offspring. Proteins related to the NR4A1/NF-κB pathway were analyzed using western blotting.ResultsThe memory and learning capacity of offspring rats was significantly reduced in the S1 and S2 groups compared to the control group (p < 0.05), while there was no obvious difference between the control and S3 groups (p > 0.05). The level of IL-1β was significantly increased (p < 0.05) in the S1 group compared with the control group. Sevoflurane anesthesia received in early and middle pregnancy could significantly affect the formation of Nissl bodies in the hippocampi of offspring rats. In addition, the expression of BDNF and CPEB2 in the hippocampi of offspring rats was greatly decreased in the S1 group compared with the control group (p < 0.05). The expression of NR4A1 in the hippocampi of rat offspring was significantly decreased in the S1 and S2 groups compared with the control group (p < 0.05). The expression of proteins related to the NF-κB pathway was increased in the S1 group compared to the control group (p < 0.05).ConclusionsThe neurotoxic effect of maternal sevoflurane anesthesia on the brain development of offspring is higher when the exposure occurs in early pregnancy than in late pregnancy, and its mechanism might involve the NR4A1/NF-κB pathway to increase the secretion of inflammatory cytokines.
Highlights
Gestation is a crucial time in the process of brain development, and it is the period most affected by external factors
Results the escape latency of the S1 group began to increase overtly on the 3rd training day (p < 0.05), the escape latency of the S2 group began to increase markedly on the 4th training day (p < 0.05), and the numbers of platform crossings in the S1 and S2 groups were significantly reduced (p < 0.05). These results demonstrated that sevoflurane exposure during early and middle pregnancy could substantially impair the later memory and learning ability of the offspring
Compared to the control group, the S1 group had a marked increase in IL-1β (p < 0.05); the expression of tumor necrosis factor (TNF)-α and IL-6 showed no significant differences among the groups (p > 0.05)
Summary
Gestation is a crucial time in the process of brain development, and it is the period most affected by external factors. The influence of prenatal factors on fetal brain development has always been a research topic of great interest. Non-obstetric surgery is needed in 0.75–2% of pregnant women, and the safety of anesthesia for mothers and children is a key consideration at this time [1]. The effectiveness and relative safety of Journal of Anesthesia (2021) 35:654–662 sevoflurane in surgical anesthesia are recognized [5]. Sevoflurane is one of the agents adopted for maintenance anesthesia during surgery on pregnant women [6, 7]. Clinical researchers are interested in further studying the effects of sevoflurane in different patient populations and organ systems
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
