VIRAL HEMORRHAGIC ENCEPHALOPATHY OF RATS II. PATHOGENESIS OF CENTRAL NERVOUS SYSTEM LESIONS123

Abstract

Cole, G. A., N. Nathanson, and H. Rivet (Johns Hopkins Univ. School of Hygiene and Public Health, Baltimore, Md. 21205). Viral hemorrhagic encephalopathy of rats. II. Pathogenesis of central nervous system lesions. Amer. J. Epid., 1970, 91: 339–350.—A study was made of the pathogenesis of hemorrhagic encephalopathy of rats produced by the HER 1 strain of rat virus (RV). HER 1 virus had an intracerebral titer in newborn rats of 10^6.55 LD₅₀ per.02 ml. Virus doses of 10^3.5 to 10^5.5 LD₆₀ produced hemorrhagic encephalopathy, and lower doses produced a fatal syndrome characterized by jaundice and runting. Rats 10 days or older underwent silent infections without apparent disease. Histological study of hemorrhagic encephalopathy in newborn rats indicated that multiple bland hemorrhages appeared throughout the central nervous system, with little or no inflammatory reaction prior to death. Hemorrhages arose from small blood vessels only; they began as foci of extravascular erythrocytes which gradually extended to form large hemorrhagic areas. Vascular infection was suggested by inclusions in the nuclei of endothelial cells, and was confirmed by immunofluores-cent staining. Infection of the vascular wall with this cytolytic virus appears to explain the hemorrhagic lesions. The other striking lesion produced in the brains of newborn rats was necrosis of external and internal granule cells of the cerebellum. Immunofiuorescent staining revealed heavy cerebellar infection confined to this group of neurons. There was some evidence that the outstanding susceptibility of granule cells was related to their rapid rate of proliferation, since the only other cellular groups which were frequently infected (peri-ventricular cells and caudate-putamen nucleus) are also known to undergo postnatal cell division in the rat.