Impact of prenatal LPS on sepsis-related neurobiological outcomes

Background early-life challenges during the prenatal period can induce persistent neurological alterations. The immature innate immune system exhibits plasticity, and appropriately timed stimuli may shape immune responses into adulthood. Objective to investigate whether prenatal exposure to lipopolysaccharide (LPS) modulates brain alterations after sepsis in adult offspring of both sexes. Methods pregnant Wistar rats received an intraperitoneal injection of LPS (100 µg/kg) on gestational day 9.5. In adulthood, offspring underwent cecal ligation and perforation (CLP) or sham surgery, generating four groups: sal+sham, LPS+sham, sal + CLP, and LPS + CLP. Survival was monitored, and behavioral assessments (open field habituation and forced swim test) were performed 10 days post-surgery. Brain regions (cortex, prefrontal cortex, hippocampus) were analyzed for cytokine levels, myeloperoxidase (MPO) activity, nitrite/nitrate (N/N) concentrations, oxidative damage, catalase (CAT) activity, and mitochondrial respiratory chain complex activities (I, II, IV). Results prenatal LPS improved survival, enhanced habituation memory (both sexes), and reduced depressive-like behavior (females). It increased IL-10 across brain regions and IL-6 in the male hippocampus, while reducing N/N in the female prefrontal cortex and hippocampus. Oxidative damage was attenuated, with reduced lipid peroxidation in the male prefrontal cortex and decreased protein carbonylation in both sexes. CAT activity increased in the male cortex and hippocampus. Prenatal LPS preserved mitochondrial complex I and IV activities in the male hippocampus, complex I in cortex and prefrontal cortex, and complex II in the female prefrontal cortex. Conclusion prenatal immune challenge with LPS confers sex-dependent neuroprotective effects, reducing inflammation, oxidative damage, and mitochondrial dysfunction induced by severe sepsis in adult offspring.