APOPTOSIS IN THE BRAINS OF INFANTS SUFFERING INTRAUTERINE CEREBRAL INJURY

This study addressed the hypothesis that ia human infants severe in ut ero insults induce a significant proportion of brain cells to undergo apoptosis, Morphologic criteria were used to quantify apoptosis and ne crosis in the cingulate gyrus of two groups of infants: six infants wh o died after severe birth asphyxia with hypoxic-ischemic encephalopath y, and six others who suffered unexpected and apparently sudden intrau terine death at or close to term. The fraction of apoptotic cells was much higher than basal levels determined in animal experiments, and wi thin both groups increased in proportion to the severity of injury as determined by total cell death (p < 0.05). The mean fraction of apopto tic cells was similar in asphyxiated infants, 8.3% (95% confidence int erval for the population, 3.7-12%), and in stillbirths, 6.7% (0.2-13.6 %). In the asphyxiated group, 20.8% (11-30.6%) of cells were necrotic, but significantly less necrosis, 3% (0.4-5.6%), was seen in stillborn infants (p < 0.05). Cell death was apoptotic after birth asphyxia in 26% (1-51%) and 78% (41-100%) in stillborn infants. In situ end labeli ng studies confirmed the presence of DNA fragmentation in apoptotic ce lls. These results demonstrate that infants who die after intrauterine insults, both those with evidence of delayed cerebral injury after hy poxia-ischemia and those without, have a significant number of cells i n the brain with the morphologic characteristics of apoptosis. They co nfirm that apoptosis contributes significantly to cerebral damage in t he perinatal period.