The role of astrocytes in the development of hepatic encephalopathy.
Thioacetamide (TAA), a hepatotoxin used to ascertain the role of astrocytes in hepatic encephalopathy, was administered to prepare four experimental groups of rats. (The TAA1D, TAA1.5D, TAA2D, and TAA2.5D group rats were perfusion fixated with formalin at 1, 1.5, 2, and 2.5 days, respectively, after initial administration of TAA. In addition, TAA was readministered to the TAA2D and TAA2.5D rats 24 h after the first dose.) Abnormalities of higher brain function and equilibrium that progressed with time were apparent in the rats receiving TAA. On the other hand, innate reflexes (e.g. pupillary reflex) were similar to those in the normal control group. Astrocyte cell areas in the hippocampus, neocortex, hypothalamus, cerebellum, and basal ganglia (striatum) from the TAA rats were significantly larger than in corresponding sites from the normal rats (maximum in TAA1D and TAA1.5D groups). However, there were no differences with respect to the midbrain. Any morphological difference was not observed in neurons between the hepatic encephalopathy and normal rats. Administration of TAA caused hepatic tissue injury that progressed over time. Surprisingly, encephalopathy was apparent even when hepatic injury was mild. These findings suggest that abnormalities in astrocytes, which precede any abnormal change in neurons, play a role in the development of hepatic encephalopathy.
Matsushita
M
M
Department of Physiology, Kansai Medical University, Moriguchi, Japan.
Yamamoto
T
T
Gemba
H
H
D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology*; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D006501:Hepatic Encephalopathy / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008099:Liver / Q000473:pathology; D008297:Male; D009474:Neurons / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide
D013853:Thioacetamide