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The Question of Astrocytic Proliferation and Mitosis in Experimentally Induced Hepatic Encephalopathy

Roger A. Brumback, MD; Lowell W. Lapham, MD

Arch Neurol. 1989;46(8):845-848.

Abstract
• 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.

Author Affiliations
From the Department of Pathology, University of Oklahoma College of Medicine and Veterans Administration Medical Center, Oklahoma City (Dr Brumback); and the Department of Pathology, University of Rochester (NY) Medical Center (Dr Lapham).

Footnotes
Accepted for publication February 16, 1989.

Read in part before the annual meeting of the American Association of Neuropathologists, Minneapolis, Minn, June 21, 1986.

Reprint requests to Department of Pathology, BMSB Room 451, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd, PO Box 26901, Oklahoma City, OK 73190 (Dr Brumback).

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