Maternal sevoflurane exposure induces neurotoxicity in offspring rats via the CB1R/CDK5/p-tau pathway

Sevoflurane is widely used for maternal anesthesia during pregnancy. Sevoflurane exposure of rats at mid-gestation can cause abnormal development of the central nervous system in their offspring. Sevoflurane is known to increase the expression of cannabinoid 1 receptor (CB1R) in the hippocampus. However, the effect of cannabinoid 1 receptor on fetal and offspring rats after maternal anesthesia is still unclear. At gestational day 14, pregnant rats were subjected to 2-h exposure to 3.5% sevoflurane or air. Rats underwent intraperitoneal injection with saline or rimonabant (1 mg/kg) 30 min prior to sevoflurane or air exposure. cannabinoid 1 receptor, cyclin-dependent kinase 5 (CDK5), p35, p25, tau, and p-tau expression in fetal brains was measured at 6, 12, and 24 h post-sevoflurane/air exposure. Neurobehavioral and Morris water maze tests were performed postnatal days 3-33. The expression of cannabinoid 1 receptor/cyclin-dependent kinase 5/p-tau and histopathological staining of brain tissues in offspring rats was observed. We found that a single exposure to sevoflurane upregulated the activity of cyclin-dependent kinase 5 and the level of p-tau via cannabinoid 1 receptor. This was accompanied by the diminished number of neurons and dendritic spines in hippocampal CA1 regions. Finally, these effects induced lower scores and platform crossing times in behavioral tests. The present study suggests that a single exposure to 3.5% sevoflurane of rats at mid-gestation impairs neurobehavioral abilities and cognitive memory in offspring. cannabinoid 1 receptor is a possible target for the amelioration of postnatal neurobehavioral ability and cognitive memory impairments induced by maternal anesthesia.

Automated summary

Sevoflurane exposure during pregnancy can lead to abnormal development of the central nervous system in offspring rats. Sevoflurane increases the expression of cannabinoid 1 receptor (CB1R) in the hippocampus, but its effects on fetal and offspring rats after maternal anesthesia are still unclear. In this study, pregnant rats were exposed to sevoflurane or air, and the expression of CB1R, cyclin-dependent kinase 5 (CDK5), and neuronal markers were observed in fetal brains. Neurobehavioral and cognitive tests were performed on the offspring, and it was found that sevoflurane exposure impaired neurobehavioral abilities and cognitive memory. CB1R may be a target for mitigating these impairments induced by maternal anesthesia.