Hypoxia associated with perinatal events can result in brain damage in the neonate. In labor and
eclampsia,
hypoxia can be intermittent, which may result in more severe damage than sustained
hypoxia. The pathogenesis of
brain injury in sustained
ischemia involves
free radical production; therefore, we investigated whether higher levels of
free radicals contribute to the greater injury induced by repetitive
ischemia. Brains were obtained from fetuses of near-term, pregnant rabbits subjected to repetitive
ischemia-reperfusion (RIR), sustained uterine
ischemia-reperfusion (IR), or a control protocol. Compared with controls, fetal brains from RIR or IR groups had more
brain edema. Brains from RIR fetuses exhibited higher levels of lipid peroxidation,
3-nitrotyrosine, and
nitrogen oxides, and lower total
antioxidant capacity and cortical cellular viability than those of IR or control fetuses. Maternal administration of
antioxidants following RIR and fetal
bradycardia resulted in lower levels of fetal cortical and hippocampal cell death. Coadministration of
Trolox and
ascorbic acid resulted in less
brain edema and liquefaction, and fewer hippocampal ischemic nuclei as compared with the saline control. Higher
free radical production may be responsible for the greater fetal
brain injury following repetitive
hypoxia-reoxygenation. Maternal
antioxidant treatment resulted in transplacental passage of
antioxidants and amelioration of
brain injury, and may be a viable clinical option following diagnosis of
fetal distress.