APOPTOSIS AND NECROSIS IN THE NEWBORN PIGLET BRAIN FOLLOWING TRANSIENT CEREBRAL HYPOXIA-ISCHEMIA

We have used a porcine model of global hypoxia-ischaemia to examine th e mode and extent of cell damage to the newborn brain. Apoptosis and n ecrosis were observed in neurons and glial cells following transient c erebral hypoxic-ischaemic injury (HII) by haematoxylin and eosin stain ing and by in situ end labelling (ISEL). Quantitative neuropathologica l analysis of the cingulate gyrus, the hippocampus and the cerebellum showed that the degree of both apoptosis and necrosis increased with t he severity of injured in these brain areas. The hippocampus and cereb ellar cortex were particularly sensitive to HII. Furthermore, some cel l types were more susceptible to a particular mode of cell death. In t he cerebellum, Purkinje cells died by necrosis but never by apoptosis. In contrast, cerebellar granule cells were frequently apoptotic, but never necrotic. In the hippo-campus, apoptosis occurred in the inner l ayer neurons of the dentate fascia and necrosis in the more mature out er layer neurons. This suggests that immature neurons may be more pron e to apoptotic death while terminally differentiated neurons die by ne crosis. Apoptosis but not necrosis was seen in cerebral white matter. This model may help to elucidate the factors that determine cell fate following HII and aid the development of cerebro-protective strategies .