Effects of sevoflurane exposure during different stages of pregnancy on the brain development of rat offspring

Abstract

Objective This study explored the effects of sevoflurane exposure during different stages of pregnancy on the brain development of offspring. Methods Thirty-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. Results The 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). Conclusions The 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.

Ex-Ovo Evaluation of Sevoflurane Exposure on Chick Embryo Development: Investigating Angiogenesis Effects

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The Promise of DNA Methylation in Understanding Multigenerational Factors in Autism Spectrum Disorders

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Effects of mid‑gestational sevoflurane and magnesium sulfate on maternal oxidative stress, inflammation and fetal brain histopathology

“…Despite the widespread use of Sv, certain studies have reported cases of neurotoxicity due to increases in neuroinflammation and oxidative stress, decreases in neuronal transmission, changes in lipid membrane fluidity and apoptosis of neuroprogenitor cells, which suggests that exposure may confer long-term adverse consequences (6)(7)(8). A number of reports have indicated that exposure to Sv, particularly during the early and mid-pregnancy periods, can also reduce postnatal learning and memory capacity (9,10). The exposure time and dose are considered the most important determinants of the activation of damage pathways by this anesthetic.…”