In vivo analysis of glial cell phenotypes during a viral demyelinating disease in mice

The time course of demyelination and remyelination in animals infected with MHV-A59 has been described else- CNP immunostaining is similar in infected (a) and control specimens (d), indicating that little destruction of myelin has occurred. However, a region at the upper left of a shows reduced immunoreactivity. 04 immunostaining is dramatically increased in the infected mouse (b) and is associated with small process bearing cells deep in white matter as well as with many radial fibers which also stain for GFAE Three white arrows in the lowest part of b have been placed around a group of cells which are strongly 04 immunoreactive but do not contain GFAP. In contrast two 04+ cells in the lower part of e (white arrows) also express GFAP. Note that their processes are thinner than those of the radially oriented astrocytes (f). Overall GFAP immunoreactivity is also slightly increased in the infected animal (c) as compared to control Or). Bar, 50 #m. l~gure 5. Spinal cord from infected mouse, 1 WPI. [3H]Thymidine was injected 2 h before killing to label the nuclei of proliferating cells, a shows Oa immunofluorescence; b is a double exposure showing GFAP by immunofluorescence and a bright field image which reveals silver grains. Three 04 positive cell bodies (a, arrows) are overlaid by silver grains (b). All three cells lack both GFAP (b) and CNP (not shown) immunoreaetivity. Other 04+ only cells (not thymidine labeled) are seen close by (fat white arrows). Bar, 10 #m. where (Woyciechowska et al., 1984; Kristensson et al., 1986; Jordan et al., 1989b) . The intensity and the evolution of lesions may vary from one animal to another as well as from one series of viral inoculation to another. Nevertheless most histopathological features follow a characteristic time sequence. Mild inflammatory lesions and very discrete areas of myelin loss are seen at 1 WPI mostly in the anterior and posterior roots. At 2 WPI, the myelin breakdown becomes apparent. Inflammatory cells infiltrate the lesions. At 3 and 4 WPI, the myelin loss is extensive with vacuolization and macrophage infiltration. At that time remyelination starts and progresses steadily in the next weeks (Jordan et al., 1989b) .