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125: Mechanisms of adverse neurological outcomes from chorioamnionitis at term

      Objective

      Infection during pregnancy conveys a significant increased risk for motor, cognitive and neurobehavioral abnormalities in the offspring. To date, research has focused on the effect of inflammation on preterm, not term, brain injury. While adverse neurological outcome is significantly increased in preterm infants, there is a growing body of data suggesting that inflammation at term is associated with increases in neurological injury, specifically cerebral palsy. The objective of this study was to elucidate whether prenatal inflammation at term results in brain injury.

      Study Design

      A mouse model of intrauterine inflammation has been utilized for these studies. At E18.5, lipolysacharide (LPS) was injected in to uterine horn (n=6); controls received no intervention (n=6). QPCR was performed to assess cytokine expression in fetal brains. Morphological changes in neurons were investigated using an established cortical culture technique. Primary neuronal cultures were established 6 hours after exposure to LPS. Confocal microscopy (NF200 and MAP2) of neuronal cultures were performed for comparison of neuronal morphology. The number of dendritic processes at division day 3 (DD3) were recorded.

      Results

      Fetal brains exposed to LPS had significanlty increased IL-1beta mRNA (12.4-fold, P=0.017), IL-6 (3.2-fold, P=0.04 and TNF-a (2.8 fold,P=0.08) compared to controls. IL-10 mRNA was not different. E18.5 LPS exposed neuronal cultures demonstrated significant morphological differences, including decreased aggregation of cells and abnormal growth of processes. On DD3, the number of dendritic processes were significantly decreased in LPS compared to control neurons (p<0.001).

      Conclusion

      Inflammation at term results in cytokine elevation in the fetal brain and altered neuronal morphology. These studies may provide a critical mechanism for the observed long term adverse neurological sequelae after exposure to inflammation at term. Further studies are needed in order to begin to develop therapeutic strategies to prevent adverse neurological outcome from inflammation at term.