Thursday, 27 March 2014

MS tissues does not look like animal autoimmune model tissue but looks like virus infection

Schuh C, Wimmer I, Hametner S, Haider L, Van Dam AM, Liblau RS, Smith KJ, Probert L, Binder CJ, Bauer J, Bradl M, Mahad D, Lassmann H. Oxidative tissue injury in multiple sclerosis is only partly reflected in experimental disease models. Acta Neuropathol. 2014 Mar 13. [Epub ahead of print]

Recent data suggest that oxidative injury may play an important role in demyelination and neurodegeneration in multiple sclerosis (MS). We compared the extent of oxidative injury in MS lesions with that in experimental models driven by different inflammatory mechanisms. It was only in a model of coronavirus-induced demyelinating encephalomyelitis that we detected an accumulation of oxidised phospholipids, which was comparable in extent to that in MS. In both, MS and coronavirus-induced encephalomyelitis, this was associated with massive microglial and macrophage activation, accompanied by the expression of the NADPH oxidase subunit p22phox but only sparse expression of inducible nitric oxide synthase (iNOS).  Acute and chronic CD4+ T cell-mediated experimental autoimmune encephalomyelitis lesions showed transient expression of p22phox and iNOS associated with inflammation. Macrophages in chronic lesions of antibody-mediated demyelinating encephalomyelitis showed lysosomal activity but very little p22phox or iNOS expressions. Active inflammatory demyelinating lesions induced by CD8+ T cells or by innate immunity showed macrophage and microglial activation together with the expression of p22phox, but low or absent iNOS reactivity.
We corroborated the differences between acute CD4+T cell-mediated experimental autoimmune encephalomyelitis and acute MS lesions via gene expression studies. Furthermore, age-dependent iron accumulation and lesion-associated iron liberation, as occurring in the human brain, were only minor in rodent brains. Our study shows that oxidative injury and its triggering mechanisms diverge in different models of rodent central nervous system inflammation. The amplification of oxidative injury, which has been suggested in MS, is only reflected to a limited degree in the studied rodent models.
So again animal tissue does not look like MS ..so what's new? Maybe the similarities with a viral infection may be telling 

3 comments:

  1. But don't you have viral models? I think I heard about murine viral encephalomyelitis

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    1. Some use Theiler's murine virus to study MS. It seems a "no brainer", no pun intended, to use the model that most represents the human disease to study the pathology and prospective treatments. Maybe studies such as this will sway further research away from EAE models.

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    2. However, if you compare apples with pears you will always get a lemon....a pathology of a week is not going to resemble something of months and years in the making.

      Models have to be usable and this is one of the reasons viral models are not used....plus a lot of effort is made to keep infections out of animal houses.

      There are a number of viral models DocotrLove used to work on one called Semliki forest virus which would cause demyelination...It was adapted to animals following its discovery in an African Country... When asked where it comes from the person said "Semliki" hence the name Semliki forest, however the translation of the word semliki means "I don't' know"...interesting anecdote:-)

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