Regional changes in kynurenic acid, quinolinic acid, and glial fibrillary acidic protein concentrations in the fetal sheep brain after experimentallyinduced placental insufficiency

OBJECTIVE: This study was undertaken to examine the effects of chronic embo lization of the umbilical circulation during late gestation on regional con centrations of quinolinic acid and kynurenic acid (neuroactive products of tryptophan catabolism) and of the astrocyte-associated glial fibrillary aci dic protein in the fetal brain. STUDY DESIGN: Pregnant ewes bearing fetuses with long-term catheter placeme nt were treated daily with injections of either saline solution (n = 4; con trol group) or mucopolysaccharide microspheres (n = 5; embolized group) int o the umbilical circulation through a femoral artery catheter between 120 a nd 140 days' gestation. The fetuses in the embolized group received suffici ent microspheres each day to reduce and maintain the femoral arterial Po-2 at less than or equal to 12 mm Hg. Autopsies were performed at 140 days' ge station to obtain the fetal brain for chemical analysis. RESULTS: Umbilical embolization resulted in nonacidemic hypoxia and hypogly cemia at 140 days' gestation. Quinolinic acid concentrations in the emboliz ed group were significantly increased in the medulla, pens, midbrain, hypot halamus, and hippocampus, whereas kynurenic acid concentrations in the embo lized group were reduced in the hippocampus and hypothalamus. There were si gnificant reductions in glial fibrillary acidic protein contents in the occ ipitoparietal cortex, hippocampus, and pens in the embolized group. CONCLUSION: Placental compromise during late pregnancy had effects on kynur enine metabolism and astrocyte function in some regions of the fetal sheep brain. We suggest that these changes increase the vulnerability of the brai n to asphyxial injury during late gestation and the perinatal period.