Axonal cytoskeleton changes in experimental optic neuritis.
Axonal loss and degeneration in multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE) have been suggested by brain imaging, pathological and axonal transport studies. Further elucidation of the processes and mechanisms 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 small number of reliable models in which the onset and location of demyelination can be well-controlled. In this study, microinjection of polyclonal rabbit anti-galactocerebroside (anti-Gal C) antibody and guinea pig complement was used to induce local demyelination in the rat optic nerve. We found that treatment with appropriate volumes of the antibody and complement could induce local demyelination with minimal pressure- or trauma-induced damage. Local changes in neurofilaments (NFs) and microtubules (MTs) were examined with both immunohistochemistry (IHC) and electron microscopy (EM). On day 1 after microinjection, we observed moderate NF and MT disassembly in the local demyelinated area, although in most cases, no apparent inflammatory cell infiltration was seen. The NF and MT changes became more apparent on days 3, 5, 7 after microinjection, along with gradually increased inflammatory cell infiltration. These results suggested that acute demyelination itself may 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, macrophages, and astrocytes, we found that most of the cells were macrophages, suggesting that macrophages may play a greater role in inflammation-related axonal degeneration and axonal loss. These results were confirmed and further characterized on the ultrastructural level.
Zhu
B
B
Department of Ophthalmology, Vancouver Hospital and Health Science Center, University of British Columbia, 2550 Willow Street, Vancouver, British Columbia, Canada. bing@ecc.ubc.ca
Moore
G R
GR
Zwimpfer
T J
TJ
Kastrukoff
L F
LF
Dyer
J K
JK
Steeves
J D
JD
Paty
D W
DW
Cynader
M S
MS
D000818:Animals; D001369:Axons / Q000648:ultrastructure*; D003599:Cytoskeleton / Q000648:ultrastructure*; D003711:Demyelinating Diseases / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D008845:Microinjections; D008854:Microscopy, Electron; D008870:Microtubules / Q000648:ultrastructure; D016900:Neurofilament Proteins / Q000648:ultrastructure; D009902:Optic Neuritis / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar
D016900:Neurofilament Proteins