Axonal cytoskeleton changes in experimental optic neuritis

Axonal loss and degeneration in multiple sclerosis (MS) and experimental al lergic encephalomyelitis (EAE) have been suggested by brain imaging, pathol ogical and axonal transport studies. Further elucidation of the processes a nd mechanism of axonal degeneration in demyelinating diseases is therefore of potential importance in order to alleviate the permanent disabilities of MS patients. However, detailed studies in this area are impeded by the sma ll number of reliable models in which the onset and location of demyelinati on can be well-controlled In this study, microinjection of polyclonal rabbi t anti-galactocerebroside (anti-Gal C) antibody and guinea pig complement w as used to induce local demyelination in the mt optic nerve. We found that treatment with appropriate volumes of the antibody and complement could ind uce local demyelination with minimal pressure- or trauma-induced damage. Lo cal changes in neurofilaments (NFs) and microtubules (MTs) were examined wi th both immunohistochemistry (MC) and electron microscopy (EM). On day 1 af ter microinjection, we observed moderate NF and MT disassembly in the local demyelinated area, although in most cases, no apparent inflammatory cell i nfiltration was seen. The NF and MT changes became more apparent on days 3, 5, 7 after microinjection, along with gradually increased inflammatory cel l infiltration. These results suggested that acute demyelination itself map induce local cytoskeleton changes in the demyelinated axons, and that the ensuing local inflammation may further enhance the axonal damage. When the lesions were stained with specific antibodies for T lymphocytes, macrophage s, and astrocytes, we found that most of the cells were macrophages, sugges ting that macrophages may play a greater role in inflammation-related axona l degeneration and axonal loss. These results were confirmed and further ch aracterized on the ultrastructural level. (C) 1999 Elsevier Science B.V. Al l rights reserved.