DELAYED NEURONAL DEATH FOLLOWING PERINATAL ASPHYXIA IN RAT

The consequences of perinatal asphyxia on the rat brain were studied 8 0 min to 8 days after birth with hematoxylin-eosin and in situ DNA dou ble-strand-breaks labeling histochemistry. Asphyxia was induced by imm ersing fetus-containing uterus horns, removed from ready-to-deliver Sp rague-Dawley rats, in a water bath at 37 degrees C for various time pe riods (0-22 min). Spontaneous- and cesarean-delivered pups were used a s controls. Perinatal asphyxia led to a decrease in the rate of surviv al, depending upon the length of the insult. No gross morphological ch anges could be seen in the brain of either control or asphyctic pups a t any of the studied time points after delivery. However, in all group s, nuclear chromatin fragmentation, corresponding to in situ detection of DNA fragmentation, was observed at different stages. Nuclear fragm entation in control pups showed a specific distribution that appeared to be related to brain maturation, thus indicating programmed cell dea th. A progressive and delayed increase in nuclear fragmentation was fo und in asphyctic pups, which was dependent upon the length of the peri natal insult. The most evident effect was seen in frontal cortex, stri atum, and cerebellum at postnatal day 8, although changes were also fo und in ventral-posterior thalamus, at days 1 and 2. Thus, nuclear chro matin fragmentation in asphyctic pups indicates a delayed post-asphyct ic neuronal death. The absence of signs of inflammation or necrosis su ggests that delayed neuronal cell death following perinatal asphyxia i s an active, apoptosis-like phenomenon.