We have previously shown that free radical production is increased in premature fetal brains following acute hypoxia in utero. We hypothesized that xanthine oxidase, an oxidant-generating enzyme, may play a role in fetal brain injury following acute hypoxia. An animal model with acute placental insufficiency from uterine ischemia was utilized for the present study. Pregnant rabbits were fed either molybdenum-deficient tungstate-supplemented diet or regular diet from day 15-28 of gestation. At day 29, the dams were subjected to intermittent periods of 10-min uterine ischemia + 2 min reperfusion (total 58 min, Repetitive), 50 min sustained ischemia (Hypoxia), or no ischemia (Control). After delivery of the fetus by hysterotomy, brain cortex and hippocampus were obtained and in vitro cellular viability determined by an investigator masked to group assignment. The wet/dry ratio of whole brains was also determined. Tungstate treatment increased cell viability in cortex and hippocampus (Table, Mean±SEM, n=5-8/group, *p<0.05, t-test.). The wet/dry ratio of brain was also significantly decreased in the tungstate treated repetitive group (n=7, 9.282±0.038) compared to regular diet repetitive group (n=10, 9.927±0.239, p<0.05, t-test). Inhibition of xanthine oxidase by tungstate-supplemented diet resulted in increased cell survival and decreased brain edema in fetal brains following acute hypoxia. Xanthine oxidase may play an important role in premature fetal brain injury following acute placental insufficiency.

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