Comparison of scrapie and transmissible mink encephalopathy in hamsters. I. Biochemical studies of brain during development of disease

Scrapie and transmissible mink encephalopathy were studied in hamsters; clinical signs, pathology, and the replication of the agents of each disease in brain and spleen were compared. The most noticeable clinical sign in scrapie-affected ham-sters was a distinct cerebellar ataxia beginning 16 weeks after inoculation. Ataxia was not prominent in animals affected with transmissible mink encephalopathy; these animals gradually became more and more lethargic. The pathology in the central nervous system in both diseases consisted of astrocytic hypertrophy, micro-vacuolation of the neuropil, and neuronal degeneration. The scrapie agent ap-peared to have a greater effect on nuclear masses, especially those present in brain stem and the central white matter of the cerebellum. The earliest lesions in both diseases were detected near pia arachnoid surfaces and adjacent to the ven-tricular system. These initial sites of involvement suggest that the cerebrospinal fluid may be an important route by which inocula are disseminated to susceptible cells after intracerebral inoculation. Both agents multiplied rapidly in brain, reach-ing titers> 108 LD50/O.05 ml before the onset of clinical signs. Titers in spleen were 4-6 logs lower than titers in brain at every point measured during the asymptomatic or clinical course of disease. Scrapie and transmissible mink encephalopathy (TME) are both classified as subacute spongi-form encephalopathies, a group which also in-cludes two human diseases, kuru and Creutzfeldt-Jakob disease. Studies to date have indicated that scrapie and TME are closely related on the basis of their clinicopathologic features and the physi-cochemical properties of their transmissible agents. We have reported the results of biochemical stud-ies of brain during the development of scrapie and TME in Syrian hamsters [1]. The present Received for publication January 17, 1974, and in re-vised form September 4, 1974. This investigation was supported in part by a post-doctoral fellowship (R.H.K.) from the National Multipl