Abstract
Abstract Evidence suggest that prenatal immune system disturbance contributes largely to the pathophysiology of neuropsychiatric disorders. A bacterial infection animal model widely accepted is administration of lipopolysaccharide (LPS). We investigated if maternal immune activation (MIA) could induce inflammatory alterations, oxidative damage and damage to blood brain barrier integrity (BBB) and placental barrier (PB) in fetal brain and pregnant Wistar rats. On gestational day 15, Wistar pregnant rats received LPS (0.25 mg/kg) to induce MIA. After 6, 12 and 24 h, fetus brain, placenta, and amniotic fluid were collected to evaluate early effects of LPS. Other group of rats from postnatal day (PND) 54 received injection of ketamine at the doses of 5, 15, and 25 mg/kg. On PND 60 rats were subjected to the spontaneous locomotor activity and pre-pulse inhibition test (PPI). MIA increased oxidative stress in the amniotic fluid and fetal brain. The BBB integrity in the hippocampus and cerebral cortex as well integrity of PB in the placenta and fetus brain were dysregulated after LPS induction. We also found elevated levels of cytokines such as interleukin (IL)-1β, IL-2, IL-4, IL-5, interferon (IFN)-γ, macrophage colony stimulating factor (M-CSF), IL-6, IL-10, IL-18, macrophage inflammatory protein (MIP)-3a, tumor necrosis factor (TNF)-α-, IL-7, MIP-1a and erythropoietin. Rats that receive MIA plus ketamine had locomotor activity impairment and a deficit in the PPI. In the present study, it was concluded that MIA increased the permeability of BBB and PB, the circulation of inflammatory mediators in fetal brains. This immune response in the prenatal period may be responsible for the behavioral changes in the adult life of offspring induced by MIA.
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