C‐Section After IL‐6 Exposure Triggers Brain Inflammation in Neonates Similar to That of Natural Delivery With or Without IL‐6 Exposure

ABSTRACT Maternal immune activation (MIA) during early to mid‐pregnancy may be associated with offspring psychological issues, while the association between MIA in late pregnancy and offspring brain inflammation remains controversial. This study investigated the effects of maternal exposure to IL‐6 during late pregnancy on brain inflammation in offspring born via different delivery methods. On gestation day 20 ± 1, pregnant rats were randomly assigned to an IL‐6 intramuscular injection group and a saline control group. Rectal temperature was monitored every half hour for 8 h postinjection. Based on spontaneous delivery within 8 h, each group was further subdivided into cesarean section and spontaneous delivery subgroups. Pregnant rats that did not deliver spontaneously underwent cesarean section to retrieve fetuses for brain inflammation assessment, while newborns from spontaneous deliveries were nursed by their mothers for 4 days. Immunohistochemistry and western blotting were used to detect Iba1, GFAP, and COX2 expression to assess brain inflammation levels in fetuses and newborns. The mode of delivery did not affect rectal temperature in pregnant rats between the IL‐6 group and the saline group. In the brain tissue of pups delivered by cesarean section, the IL‐6 group exhibited significantly higher expression levels of Iba1, GFAP, and COX2 compared with the control group, while no significant difference was observed between the two groups in pups delivered vaginally. In both groups of newborn rats delivered vaginally, GFAP and COX2 expression increased on Day 2, peaked on Day 3, and decreased on Day 4, while Iba1 expression peaked on Day 4. Maternal inflammation and the stimuli of natural birth can both induce brain inflammation in fetal or newborn rats. Maternal inflammation during late pregnancy has a moderate effect on fetuses, comparable to the effects observed after natural birth.