"Microglial nodules" and "newly forming lesions" may be a Janus face of early MS lesions; implications from virus-induced demyelination, the Inside-Out model.
BACKGROUND
Although the precise mechanism of initial lesion development in multiple sclerosis (MS) remains unclear, two different neuropathological findings have been reported as a potential early pathology of MS: "microglial nodules" and "newly forming lesions", both of which contain neither T cell infiltration nor demyelination. In microglial nodules, damaged axons were associated with a small number of aggregated macrophages/microglia, while oligodendrocyte apoptosis was a characteristic in newly forming lesions. However, is the presence of "microglial nodules" and "oligodendrogliopathy" mutually exclusive? Might these two different observations be the same neuropathology (as proposed by the concept, "preactive lesions"), but interpreted differently based on the different theories of early MS lesion development, using different staining methods?


CONCLUSIONS
Since two studies are looking at two distinct aspects of early MS pathogenesis (one focused on axons and the other on oligodendrocytes), in a sense, one can say that these two studies are complementary. On the other hand, experimentally, Wallerian degeneration (WD) has been demonstrated to induce both microglial nodules and oligodendrocyte apoptosis in the central nervous system (CNS). Here, when encephalitogenic T cells are present in the periphery in both autoimmune and viral models of MS, induction of WD in the CNS has been shown to result in the recruitment of T cells along the degenerated tract, leading to demyelination (Inside-Out model). These experimental findings are consistent with early MS pathology described by both "microglial nodules" and "newly forming lesions".


CONCLUSIONS
The differences between the two neuropathological findings may be based on the preference of staining methods, where one group observed axonal and microglial pathology and the other observed oligodendrocyte apoptosis; a Janus face that is looked at from the two different sides.
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA. fsato@lsuhsc.edu.|Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA. fsato@lsuhsc.edu.
Fumitaka
F
Sato
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA. nemartin@tepper.cmu.edu.|Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA. nemartin@tepper.cmu.edu.
Nicholas E
NE
Martinez
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA. eclibu@lsuhsc.edu.|Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA. eclibu@lsuhsc.edu.
Elaine Cliburn
EC
Stewart
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA. somura@lsuhsc.edu.|Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA. somura@lsuhsc.edu.
Seiichi
S
Omura
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA. JAlexa@lsuhsc.edu.|Department of Neurology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA. JAlexa@lsuhsc.edu.
J Steven
JS
Alexander
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA. itsuno@lsuhsc.edu.|Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA. itsuno@lsuhsc.edu.|Department of Neurology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA. itsuno@lsuhsc.edu.
Ikuo
I
Tsunoda
D000818:Animals; D001369:Axons / Q000473:pathology*; D006801:Humans; D017628:Microglia / Q000473:pathology*; D008959:Models, Neurological; D009103:Multiple Sclerosis / Q000473:pathology*; D009836:Oligodendroglia / Q000473:pathology*