Axonal injury heralds virus-induced demyelination.
Axonal pathology has been highlighted as a cause of neurological disability in multiple sclerosis. The Daniels (DA) strain of Theiler's murine encephalomyelitis virus infects the gray matter of the central nervous system of mice during the acute phase and persistently infects the white matter of the spinal cord during the chronic phase, leading to demyelination. This experimental infection has been used as an animal model for multiple sclerosis. The GDVII strain causes an acute fatal polioencephalomyelitis without demyelination. Injured axons were detected in normal appearing white matter at 1 week after infection with DA virus by immunohistochemistry using antibodies specific for neurofilament protein. The number of damaged axons increased throughout time. By 2 and 3 weeks after infection, injured axons were accompanied by parenchymal infiltration of Ricinus communis agglutinin I(+) microglia/macrophages, but never associated with perivascular T-cell infiltration or obvious demyelination until the chronic phase. GDVII virus infection resulted in severe axonal injury in normal appearing white matter at 1 week after infection, without the presence of macrophages, T cells, or viral antigen-positive cells. The distribution of axonal injury observed during the early phase corresponded to regions where subsequent demyelination occurs during the chronic phase. The results suggest that axonal injury might herald or trigger demyelination.
Tsunoda
Ikuo
I
Department of Neurology, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.
Kuang
Li-Qing
LQ
Libbey
Jane E
JE
Fujinami
Robert S
RS
D000818:Animals; D001369:Axons / Q000473:pathology* / Q000821:virology*; D018188:Cardiovirus Infections / Q000473:pathology*; D003711:Demyelinating Diseases / Q000473:pathology* / Q000821:virology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007249:Inflammation; D051379:Mice; D008815:Mice, Inbred Strains; D008856:Microscopy, Fluorescence; D009103:Multiple Sclerosis / Q000473:pathology; D017945:Theilovirus