Electron micrographic analysis of demyelination and axonal loss in DM- and NDM-infected mouse spinal cord. Representative foci of demyelination and axonal injury were selected from the toluidine blue-stained sections shown in Figure 3 and processed for electron microscopy. (a) Normal morphology of myelinated axons was exhibited from a non plaque region adjacent to a demyelinated plaque of DM-infected mouse spinal cord. (b–d) Demyelinating plaque in DM-infected mouse spinal cord showed extensive loss of myelin, hypomyelination (arrows), complete axonal degeneration with only residual empty vacuoles (arrowheads), naked axons with no myelin sheath at all (), and macrophages (M). (e) A high-magnification image (120,000x) of a naked axon surrounded only by a single lipid bilayer shows preservation of cytoskeleton elements (microtubules and intermediate filaments). (f) In contrast, NDM-infected mouse spinal cords show only rare examples of early axonal degeneration. Marks an oligodendrocyte nucleus. Such early axonal degeneration was not observed in mock-infected mice. Original magnifications: (a) 3000x, (b) 5000x, (c) 6000x, (d) 3000x, (e) 120,000x, and (f) 6000x. (Adapted from the work of [73]).