Cell death in perinatal hypoxic-ischaemic 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 nuclei in the pons, is a common pattern of injury in mature perinatal deaths. Other evidence implicates apoptosis in hypoxic brain injury. In this study the mode of cell death in hypoxic injury was investigated in 11 fresh stillbirths and 10 neonatal deaths. Sections of pons were stained using several methods including terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL) and immunocytochemistry. Karyorrhectic nuclei were counted on adjacent haemotoxylin and eosin sections. A high percentage of apoptotic cells was significantly associated with the presence of karyorrhexis in the pons, but there were five stillbirths in whom apoptosis in the pons was the sole evidence of hypoxic brain injury. PCNA positive neuronal nuclei were seen in 19 out of 21 cases. The results suggest that both apoptosis and necrosis are occurring following hypoxic injury, so that the pattern of injury in the pons may be better termed 'selective neuronal death'. Variations in severity and duration of the insult might explain the differences between cases. The presence of PCNA-positive neurons may suggest DNA repair in these nuclei, which might be activated at an early stage of apoptosis. However the precise mechanism by which apoptosis is induced in hypoxic brain injury remains to be elucidated.