Increased Brain Levels of F2-Isoprostane Are an Early Marker of Behavioral Sequels in a Rat Model of Global Perinatal Asphyxia

Abstract

Perinatal asphyxia is a major cause of immediate and postponed brain damage in the newborn. It may be responsible for several delayed neurologic disorders and, in this respect, early markers of brain injury would be relevant for therapeutic intervention as well as for identification of infants at high risk for developmental disabilities. Biochemical measurements (brain F 2-isoprostane levels) and behavioral tests (ultrasonic vocalization pattern on postnatal days (pnd) 5, 8, and 11, spontaneous motor behaviors on pnd 7 and 12, and homing response on pnd 10) were performed in a rat model of global perinatal asphyxia in the immature neonate. Caesarean section was performed in rats and the pups, still in uterus horns, were placed into a water bath at 37°C for either 10 or 20 min. Caesarean delivered pups were used as controls. Pups experiencing severe (20 min), in contrast to those undergoing the 10 min, asphyctic insult presented with detectable abnormalities including early (two hours after the insult) increase in brain F2-isoprostane (a direct marker of oxidative injury) without detectable changes in PGE 2, COX-2 and iNOS levels, and delayed physical (reduced weight gain on pnd 5 and thereafter) and behavioral disturbances (alterations in ultrasound emission on pnd 11 and spontaneous motricity levels mainly). These findings suggest that increased brain F2-isoprostane levels shortly after the asphyctic insult are predictive of delayed behavioral disturbances in the newborn rat. The present 20-min asphyxia model might serve for the assessment of preventive and curative strategies to treat neurologic/behavioral disturbances associated with perinatal asphyxia.