Intrauterine infection promotes brain region specific cytokine activation and hyperactivity in developing rat

摘要

Intrauterine infection during pregnancy is associated with premature birth, periventricular leukomalacia, early activation of the fetal immune system and poor neurodevelopmental outcomes. Previous clinical studies and studies with animal models have shown increased activation of the immune system evidenced by increased levels of inflammatory cytokines, white matter damage and delays in behavioral development. Animal models of intrauterine infection with consistent behavioral results, white matter damage and immune activation have been difficult to validate. Using a rodent model of intrauterine infection, we examined neurobehavioral development and locomotor development in the resulting pups, and measured inflammatory cytokines in the striatum, frontal cortex and cerebellum. Pregnant rats at gestational day 17 were inoculated with 1 × 105?colony forming units of?Escherichia coli?or 0.1 ml of saline. Intrauterine infection led to a significant increase in the expression of interleukin 1 β, interleukin-6 and tumor necrosis factor-α.?E. coli?injection increased walking, turning and overall motor activity in rats. In summary, the results of this study indicate that?E. coli?induced intrauterine infection resulted in neuroinflammation and led to hyperactivity in basic locomotion.