I thought that gathering opinions and evidence that only counter the autoimmune hypothesis, without necessarily presenting some other cause for MS, could be useful.
If MS is an autoimmune disease a particularly informative setting for studying this would be in patients who have MS and are concomitantly infected with HIV infection, a situation which is known to induce a severe state of immune deficiency. Berger et al. reported seven such patients, six of whom developed an immunodeficient state after HIV infection but who continued to have relapsing-remitting MS....These data would
argue strongly against any autoimmune aetiology, i.e.T-cell mediated autoimmune pathogenesis. (Behan et al. 2002)
I am guessing you meant this one?notasperfectasyou wrote:that use something involving something like copper sulfate, or something that sounds like that but with more syllables
The cuprizone model is a model for toxic demyelination. In this model, young mice are fed with the copper chelator cuprizone, leading to oligodendrocyte death and a subsequent reversible demyelination. Spontaneous remyelination can be seen as early as 4 days after withdrawal of cuprizone.
http://www.ajnr.org/cgi/content/full/28/1/190Lyon wrote:Interesting Ken. I looked all over heck and find assorted variants of the EAE model, but ......they are all variants of EAE??
The most common experimental models for multiple sclerosis can be described as immune-mediated or virus-induced, and these distinctions form the basis for the organization of the book into 4 sections. The first and longest section covers "Experimental Allergic (Autoimmune) Encephalomyelitis (EAE)." In these 576 pages and 27 chapters, EAE is given a comprehensive treatment, including history, histopathology, genetics, roles of individual cell types and processes, and a single section devoted to EAE in primates. The second section devotes 119 pages and 9 chapters to "Theiler’s Murine Encephalomyelitis Virus (TMEV)–Induced Demyelination." The 139 pages and 13 chapters of the third section cover "Corona Virus–Induced Demyelination," and the final shorter section has 1 chapter each on "Semliki Forest Virus-Induced Demyelination" and canine distemper virus–induced demyelination.
Demyelination in a transgenic mouse: A model for multiple sclerosis
A transgenic mouse containing 70 copies (ND4) of the transgene encoding DM20, a myelin proteolipid protein, appeared clinically normal up to 3 months of age. By 8-10 months, it showed tremors, unsteady gait, and dies shortly thereafter. We concluded that the clinical symptoms correlated with demyelination based on the following criteria: (1) at 10 months of age only 17% of the amount of myelin obtained from normal mice was isolated from the ND4 mice; (2) astrogliosis, a prominent feature of demyelinating disease was minimal at 3 months of age but prominent by 10 months; (3) at the electron microscopic level disrupted myelin was seen at 8 months of age in the ND4 mice and ingested myelin debris was found in astrocytes; (4) lymphocytic infiltration in association with endothelial cells was observed routinely in the ND4 mice; (5) sections through optic nerves showed denuded and thinly myelinated axons in the 8 month old ND4 mice.
Although the mechanism by which demyelination takes place is not fully understood, measurements of the amounts of PLP suggest it is down-regulated by the large amount of DM20. Since DM20 is a major proteolipid in the young but a minor one in the adult, the persistence of high levels in the adult results in improperly assembled myelin which is prone to disruption. Therefore demyelination in the ND4 mouse appears to result from the persistence of immature myelin into the adult. © 1993 Wiley-Liss, Inc.
Not at all, I thought EAE was induced auto-reactivity to myelin, but i don't know if it was virus induced(and still don't?); and hence it would actually give some substantiation to your statement that they were all EAE variants. The quote I supplied appears to group EAE in with the other virus induced demylinating models. I was just too lazy/uninterested to do the search for myself.Lyon wrote:You aren't hinting that I'm fallible are you?
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