Hyperthermia amplifies brain cytokine and reactive oxygen species response in a model of perinatal inflammation

Abstract

Chorioamnionitis, a perinatal infection of the fetal membranes, and maternal fever, which often accompanies infection are both risk factors for cerebral palsy (CP). Inflammation is a typical reaction to infection. Thus the aim of this study was to determine if hyperthermia alters newborn rat brain inflammatory response and oxidant stress after a maternal rat lipopolysaccaharide (LPS) injection. Since chorioamnionitis can predispose the fetus to perinatal hypoxia, we also explored the interaction with postnatal hypoxia. Exposure of newborn pups to brief hypoxia alone significantly increased brain tumor necrosis factor-α (TNF-α) and slightly increased levels of nitrite/nitrate. When maternal LPS was combined with postnatal hypoxia, the levels of TNF-α in were further increased when compared with hypoxia alone. Exposure of newborn pups to hyperthermia at 39 °C following maternal LPS and hypoxia caused yet more significant increases in brain TNF-α, nitrite/nitrate, and MDA/4-HAD compared to that under normal temperature conditions. This study supports the hypothesis that fever is a significant modifier of brain inflammatory response in developing brain particularly in a setting of hypoxia.