CELL-DEATH IN PERINATAL HYPOXIC-ISCHEMIC BRAIN INJURY

Perinatal hypoxic brain injury is a major cause of death and morbidity , in which the onset of injury can be prenatal, and the effects may be delayed, Selective neuronal necrosis, with isolated karyorrhectic nuc lei in the pens, is a common pattern of injury in mature perinatal dea ths. Other evidence implicates apoptosis In hypoxic brain injury. In t his study the mode of cell death in hypoxic injury was investigated in II fresh stillbirths and 10 neonatal deaths. Sections of pens were st ained using several methods including terminal deoxynucleotidyl transf erase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelli ng (TUNEL) and immunocytochemistry. Karyorrhectic nuclei were counted on adjacent haematoxylin and eosin sections. A high percentage of apop totic cells was significantly associated with the presence of karyorrh exis in the pens, but there were five stillbirths in whom apoptosis in the pens was the sole evidence of hypoxic brain injury. PCNA positive neuronal nuclei were seen in 19 out of the 21 cases. The results sugg est that both apoptosis and necrosis are occurring following hypoxic i njury, so that the pattern of injury in the pens may be better termed 'selective neuronal death'. Variations in severity and duration of the insult might explain the differences between cases. The presence of P CNA-positive neurons may suggest DNA repair in these nuclei, which mig ht be activated at an early stage of apoptosis. However the precise me chanism by which apoptosis is induced in hypoxic brain injury remains to be elucidated.