dinoprost and Leukomalacia--Periventricular

Our aim was to assess the plasma free 8-epi-prostaglandin F(2alpha) (8-isoprostane) and ascorbyl radical as risk indicators for oxidative damage in extremely low birth weight infants (ELBWIs) and the effect of N-acetylcysteine (NAC) on these markers. Plasma samples were collected on days 3 and 7 of life from infants who were enrolled in a randomized, controlled trial in which i.v. NAC or placebo was administered to ELBWIs during the first week of life, with the aim of preventing bronchopulmonary dysplasia (BPD). Plasma 8-isoprostane was analyzed in 83 infants using an enzyme immunoassay kit. Ascorbyl radical concentration was measured in 61 infants with electron spin resonance spectroscopy. The 8-isoprostane concentrations were similar in the NAC and placebo groups. In infants who later developed BPD or died (n = 29), the median (range) 8-isoprostane concentration was significantly higher (p = 0.001) on day 3 and day 7 [50.0 pg/mL (19-360) and 57.0 pg/mL (14-460), respectively] than in survivors without BPD [n = 54; 34.5 pg/mL (5-240) and 39.5 pg/mL (7-400), respectively]. The 8-isoprostane levels increased significantly more (p < 0.05) in infants who later developed periventricular leukomalacia. NAC treatment or the later development of BPD was not related to the ascorbyl radical levels. The ascorbyl radical level decreased significantly in all groups from day 3 to day 7, but the difference between the groups was not significant. The mean (SD) ascorbyl radical level on day 3 was significantly higher (p < 0.01) in infants who later developed periventricular leukomalacia [287 (124) versus 194 (90)]. These data suggest that plasma 8-isoprostane could serve as a marker in assessing the risk for BPD development in ELBWIs.

Topics: Biomarkers; Bronchopulmonary Dysplasia; Dehydroascorbic Acid; Dinoprost; Female; Humans; Infant, Newborn; Infant, Premature; Leukomalacia, Periventricular; Male; Oxidative Stress

The premature infant is at increased risk of cerebral white matter injury. Melatonin is neuroprotective in adult models of focal cerebral ischemia and attenuates ibotenate-induced white matter cysts in neonatal mice. Clinically, melatonin has been used to treat sleep disorders in children without major side effects. The aim of this study was to investigate the protective and anti-inflammatory effects of melatonin in the immature brain following intrauterine asphyxia. Fetal sheep at 90 d of gestation were subjected to umbilical cord occlusion. Melatonin (20 mg/kg, n = 9) or vehicle (n = 10) was administered IV to the fetus, starting 10 min after the start of reperfusion and continued for 6 h. Melatonin treatment resulted in a slower recovery of fetal blood pressure following umbilical cord occlusion, but without changes in fetal heart rate, acid base status or mortality. The production of 8-isoprostanes following umbilical cord occlusion was attenuated and there was a reduction in the number of activated microglia cells and TUNEL-positive cells in melatonin treated fetuses, suggesting a protective effect of melatonin. In conclusion, this study shows that melatonin attenuates cell death in the fetal brain in association with a reduced inflammatory response in the blood and the brain following intrauterine asphyxia in mid-gestation fetal sheep.

Topics: Animals; Anti-Inflammatory Agents; Asphyxia; Blood Gas Analysis; Blood Pressure; Brain; Cell Death; Dinoprost; Female; Fetal Diseases; Gestational Age; Heart Rate, Fetal; Humans; Infant, Newborn; Leukomalacia, Periventricular; Melatonin; Neuroprotective Agents; Pregnancy; Sheep; Sulfhydryl Compounds; Time Factors; Umbilical Cord