DNA synthesis in Alzheimer type II astrocytosis. The question of astrocytic proliferation and mitosis in experimentally induced hepatic encephalopathy
R. A. Brumback and L. W. Lapham
Department of Pathology, University of Oklahoma College of Medicine, Oklahoma City.
Hepatic encephalopathy is associated with development of Alzheimer type II
astrocytosis consisting of large, pale, frequently paired astrocytic
nuclei. Previous studies have suggested that the paired forms are a
manifestation of astrocytic proliferation and that the two nuclei of paired
forms are in separate cells and have an equal (diploid) DNA complement. A
model of hepatic encephalopathy can be produced using methionine
sulfoximine to inhibit irreversibly the enzyme glutamine synthetase,
resulting in elevated brain ammonia levels and development of Alzheimer
type II astrocytosis. Using this model Sprague-Dawley rats were
simultaneously injected with methionine sulfoximine 300 mg/kg and tritiated
thymidine 15 mCi/kg. Autoradiography of cerebral sections from animals
killed 18 to 36 hours after the injection revealed many heavily labeled
cortical Alzheimer type II astrocytic nuclei. These findings are consistent
with DNA synthesis and mitotic division of Alzheimer type II astrocytes.
