Brain hypoxia studied in mouse central nervous system cultures. I. Sequential cellular changes.

Heavily myelinated cultures of newborn mouse cerebellum were exposed to hypoxia and studied by electron microscopy. The cultures were placed in an incubating medium deprived of oxygen (95 to 97 per cent deprivation) for 7 to 60 minutes and fixed immediately for electron microscopy. The amount of oxygen present in the medium and time course of hypoxia were constantly monitored and recorded by an oxygen probe of polarographic oxygen sensor type and a recorder. In contrast to previous in vivo studies, this in vitro model of hypoxic cell injury has provided accurate information concerning the relationship between degree of hypoxia and cell lesion. Hypoxia affected neurons which showed "swelling" and disorganization of cristae in mitochondria and reduced cytoplasmic matrix density due to the dispersion of polysomes. A small population of neurons with an increased cytoplasmic density and "swollen" mitochondria was also noted. Clearing and degeneration of presynaptic terminals and postsynaptic dendrites were observed. After a longer period of hypoxia most neurons showed an extensive degenerative change consisting of rarefaction of cytoplasm and loss of cytoplasmic organelles. In contrast to neuronal changes, no structural alteration was observed in astrocytes and oligodendrocytes.