3 research outputs found
Effects of intra-amniotic lipopolysaccharide and maternal betamethasone on brain inflammation in fetal sheep
Rationale: Chorioamnionitis and antenatal glucocorticoids are common exposures for preterm infants and can affect the fetal brain, contributing to cognitive and motor deficits in preterm infants. The effects of antenatal glucocorticoids on the brain in the setting of chorioamnionitis are unknown. We hypothesized that antenatal glucocorticoids would modulate inflammation in the brain and prevent hippocampal and white matter injury after intra-amniotic lipopolysaccharide (LPS) exposure. Methods: Time-mated ewes received saline (control), an intra-amniotic injection of 10 mg LPS at 106d GA or 113d GA, maternal intra-muscular betamethasone (0.5 mg/kg maternal weight) alone at 113d GA, betamethasone at 106d GA before LPS or betamethasone at 113d GA after LPS. Animals were delivered at 120d GA (term=150d). Brain structure volumes were measured on T2-weighted MRI images. The subcortical white matter (SCWM), periventricular white matter (PVWM) and hippocampus were analyzed for microglia, astrocytes, apoptosis, proliferation, myelin and pre-synaptic vesicles. Results: LPS and/or betamethasone exposure at different time-points during gestation did not alter brain structure volumes on MRI. Betamethasone alone did not alter any of the measurements. Intra-amniotic LPS at 106d or 113d GA induced inflammation as indicated by increased microglial and astrocyte recruitment which was paralleled by increased apoptosis and hypomyelination in the SCWM and decreased synaptophysin density in the hippocampus. Betamethasone before the LPS exposure at 113d GA prevented microglial activation and the decrease in synaptophysin. Betamethasone after LPS exposure increased microglial infiltration and apoptosis. Conclusion: Intra-uterine LPS exposure for 7d or 14d before delivery induced inflammation and injury in the fetal white matter and hippocampus. Antenatal glucocorticoids aggravated the inflammatory changes in the brain caused by pre-existing intra-amniotic inflammation. Antenatal glucocorticoids prior to LPS reduced the effects of intra-uterine inflammation on the brain. The timing of glucocorticoid administration in the setting of chorioamnionitis can alter outcomes for the fetal brain
The identification and significance of pure sediment-derived granites
© 2017 The Author(s)The characterization of the geochemical reservoirs of the Earth's continental crust, including the determination of representative upper and lower crustal compositions, underpins our understanding of crustal evolution. The classic I- and S-type granite classification has often been invoked to distinguish between melts derived from igneous protoliths and those derived from the melting of a sedimentary source. Recent geochemical studies suggest that most granites, even those cited as typical examples of ‘S-type’, show evidence for a mixture of mantle and upper crustal sources, thereby implying that granite formation is evidence for overall crustal growth. We have examined the source of leucogranite bodies in one of the world's youngest collisional orogens using novel zircon techniques that can resolve the presence of even minor mantle contributions. 232 zircons from 12 granites from the Bhutan Himalaya were analysed by in-situ techniques for O, Hf and U–Pb isotopic signatures. In combination with data from the granite host rocks, our data show that the Himalayan leucogranites were derived solely from metamorphosed crustal sediments, and do not record any mantle contribution. This finding is consistent with the time-lag between crustal thickening and widespread crustal melting, and the heat-producing capacities of the pelitic source rocks. We conclude that Himalayan leucogranites provide a more suitable type locality for ‘S-type’ granites than the Lachlan area in South-East Australia where the term was first defined. The Himalayan leucogranites therefore provide evidence that syn-orogenic melting during collisional events does not necessarily result in crustal growth. Importantly, crustal growth models should not always assume that crustal growth is achieved during collisional orogenesis