Neuron death and glial response in pontosubicular necrosis. The role of the growth inhibition factor

Abstract

Aim and methods: Fluorochrome and immunohistochemical studies were performed on neonates with pontosubicular necrosis (PSN), aged 26 - 42 weeks of gestation (GW), compared with preterm and term controls aged from 10 GW to 3 months of age.

Results: A fluorochrome study using a confocal microscope revealed that nuclear DNA changes occurred earlier than cytoplasm degeneration with diminished RNA orange-red fluorescence. These changes were restricted to the small immature neurons in the pons and subiculum with PSN. On the other hand, although glial fibrillary acidic protein-positive reactive astrocytes were not increased in number, growth inhibitory factor- (GIF) immunoreactive glia with vesicular large nuclei were increased in number within the gray matter of the pons, subiculum, and cerebral cortex in the PSN group. The nuclei of GIF-containing astrocytes became round and vesicular, nearly twice in size and increased in number. Thus, the neuronal death began at the nuclei of selective neurons in specific areas in PSN, although GIFcontaining astrocytes were increased in widespread areas.

Conclusion: These facts suggest that immature neurons in the pontine nuclei and subiculum are selectively vulnerable to some insults such as hypocarbia and hyperoxygenation, and PSN involves a possible apoptotic neuron death mechanism and a characteristic glial response.