The effects of trans-cinnamic acid on cognitive-behavioral functions, neuroinflammation, oxidative damage, and the AKT/GSK3β signaling pathway in hippocampus of offspring rats from a preeclampsia model.

Preeclampsia (PE) is a pregnancy-related disorder characterized by hypertension and proteinuria, which can lead to fetal neuroinflammation and long-term neonatal issues. This study examines the anti-inflammatory and neuroprotective effects of cinnamic acid (CA) in a rat model of L-NAME-induced PE. Twenty pregnant Wistar rats were randomly assigned to four groups: a control group (no treatment), a PE + NS group (receiving daily subcutaneous injections of 125 mg L-NAME from gestational day 13-21, followed by oral saline one hour later), and CA treatment groups (PE+CA50 and PE+CA100, receiving oral CA (50 or 100 mg) one hour after L-NAME injection). Behavioral assessments-including working memory, passive avoidance learning, and anxiety-like behaviors-were conducted on postnatal day (PND) 30. On PND42, hippocampal levels of oxidative stress markers, pro- and anti-inflammatory cytokines, AKT/GSK-3β expression, and cellular density in the CA1 and CA3 regions were measured. Notably, the CA-treated groups showed significant improvements in working and avoidance memory, reduced anxiety-like behaviors, and decreases in 8-hydroxy-2'-deoxyguanosine (8-OHdG), protein carbonyl (PC), 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, and GSK-3β. Additionally, IL-10 and AKT levels increased, while dark neuronal density in the CA1 and CA3 regions decreased in these groups compared to PE + NS. Overall, CA modulated the AKT/GSK-3β signaling pathway, reduced pro-inflammatory cytokines and oxidative stress, mitigated neuronal damage, and improved cognitive and behavioral outcomes in juvenile offspring rats exposed to the PE model.