Chapter B 1 HISTOPATHOLOGY IN THE THEILER'S VIRUS MODEL OF DEMYELINATION Ure, D. R. and Rodriguez, M. Deparments of Neurology and Immunology, Mayo Medical and Graduate School, Rochester, MN Abstract: Key words: The Theiler's virus model shows all the major features of MS pathology - demyelination, inflammation, axonal injury, and remyelination. Extensive qualitative and quantitative characterization of the pathology has provided important insights into disease mechanisms, particularly how they relate to neurological function. Theiler's virus, histopathology, demyelination, multiple sclerosis Among the viral models of MS, one of the best characterized is inflammatory demyelination in the mouse CNS induced by Theiler's murine encephalomyelitis virus (TMEV). A primary reason why the TMEV model is relevant to MS is the similarities in pathology between the two diseases. Both are characterized by inflammation, demyelination, axonal injury, and remyelination to varying degrees. Each of these pathological features varies widely and somewhat independently in the TMEV model, largely as a result of mouse strain. This chapter will focus primarily on the spinal cord pathology in the SJL mouse strain following infection with the Daniel's strain of TMEV. SJL mice develop inflammatory demyelination in the spinal cord and brainstem starting at 3 weeks postinfection (pi). It persists for the life of the mouse, accompanied by extensive axonal injury, minimal remyelination, and progressive accumulation of neurological deficits - a model of chronic, progressive MS. This disease differs in important ways from that induced by the closely related BeAn strain of virus, which includes infected cell types, pathology, and disease course. Dal Canto, Lipton, and colleagues provided many of the early descriptions of TMEV pathology. In the past decade our laboratory has extended these observations, but more importantly we have analyzed each of the major pathological features quantitatively and related them to motor dysfunction.