Perinatal asphyxia induced neuronal loss by apoptosis in the neonatal rat striatum: a combined TUNEL and stereological study.

Perinatal asphyxia can lead to cell damage in various regions of the brain, such as the neostriatum. In this study, we investigated the mechanism of cell death that leads to neuron loss in the neostriatum of rat pups. Asphyxia was induced by immersing fetus-containing uterus horns in a water bath at 37 degrees C for 20 min. This led to an increase in mortality rate (+/- 40%) compared to control pups (0%). TUNEL-positive cell profiles were visible in all groups at postnatal day (P) 2, P8, and P15, peaking at P8. A significant increase of 40% at P8 and 45% at P15 in the number of TUNEL-positive cell profiles was observed in asphyctic rats compared to control rats. Nuclear condensation and fragmentation was visible with the DNA stain Hoechst 33342. Furthermore, laser-scanning confocal microscopy showed multiple DNA fragments in TUNEL-positive cell profiles. We found a decrease of 16% in the total number of striatal neurons in the asphyctic pups compared to the control pups at 21 days postasphyxia using stereology. These data show that asphyxia causes exaggerated apoptotic cell death during the first week of life and as a consequence a small amount of neuron loss in the neostriatum.