Morphologic effects of ammonia on primary astrocyte cultures. I. Light microscopic studies

To evaluate the astrocytic alterations commonly seen in hepatic encephalopathy and other hyperammonemic states, primary astrocyte cultures derived from neonatal rats were exposed to varying concentrations of ammonia for one to ten days. Ammonia-treated cultures initially showed an increase in basophilia, prominent cytoplasmic processes and increased cytoplasmic granularity and vacuolization. Nucleoli were increased in size and there was an increase in nucleolar/nuclear ratio. Later, fragmentation and loss of cytoplasmic processes, formation of dense bodies and frank cellular disintegration were noted. The changes were proportional to the concentration and duration of ammonia treatment. Our studies show that ammonia is capable of directly causing morphologic alterations in astrocytes. We believe that the use of primary cultures provides a means of exploring the precise role of astrocytes in hyperammonemic states.