inside-out and outside-in models

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frodo
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inside-out and outside-in models

Post by frodo »

I reproduce here below an article that I have found with a comparison about the main two families of theoretical models for MS. Inside-out and Outside-in, meaning if MS begins outside of the CNS (behind the BBB) or inside it.

I suppose that CCSVI would be in the outside-in family, together with the classic models. Something in the blood, outside the CNS, destroys the BBB. But there is other possibility. That something from the inside attacks the BBB, and later the demyelination process happens as the normal theory explains.

I would like to hear your thoughts. This is the article.

http://multiple-sclerosis-research.blog ... nd-up.html

Multiple sclerosis (MS) is considered to be an autoimmune, inflammatory disease of the CNS. In most patients, the disease follows a relapsing–remitting course and is characterized by dynamic inflammatory demyelinating lesions in the CNS. Although on the surface MS may appear consistent with a primary autoimmune disease, questions have been raised as to whether inflammation and/or autoimmunity are really at the root of the disease, and it has been proposed that MS might in fact be a degenerative disorder. We argue that MS may be an 'immunological convolution' between an underlying primary degenerative disorder and the host's aberrant immune response. To better understand this disease, we might need to consider non-inflammatory primary progressive MS as the 'real' MS, with inflammatory forms reflecting secondary, albeit very important, reactions.

Traditionally, multiple sclerosis (MS) has been considered to be an autoimmune disease in which dysregulated auto-reactive T cells in the periphery cross into the CNS and, together with macrophages and B cells, proceed to destroy various CNS elements. The resulting inflammatory reaction, which typically follows a relapsing–remitting clinical course in the initial stages, causes further demyelination and tissue injury. Such an 'outside-in' model is being challenged by a competing view that argues that the initial malfunction occurs within the CNS, similarly to other neurodegenerative disorders. This alternative, 'inside-out' model argues that a primary cytodegeneration (possibly focused on the oligodendrocyte–myelin complex) is the initial event, and by releasing highly antigenic constituents, secondarily promotes an autoimmune and inflammatory response in the predisposed host, possibly further driving degeneration. Some people think that the inflammatory response just comes in to clear the debris up in some form of "protective immunity" This review suggests that MS is a neurodegenerative disease underlying whose clinical course is influenced by relapses.

The "outside-in" of myelin basic protein induced autoimmunity is probably a load of guff that has been perpetuated by Fundamentalist Immunologists fixated on some form of EAE. These people have brain-washed the masses with their ideas that largely do not fit many of the realities of MS.
Last edited by frodo on Thu May 14, 2015 12:08 pm, edited 1 time in total.
Cece
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Re: inside-out and outside-in models

Post by Cece »

CCSVI model could be combination of outside-in and inside-out: Outside-in because of shear stress damage to the blood-brain barrier, but inside-out because of the starvation and hypoxia of the brain due to impaired transfer of nutrients and oxygen due to deranged flow. The initial event, however, remains outside.
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frodo
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Re: inside-out and outside-in models

Post by frodo »

Cece wrote:CCSVI model could be combination of outside-in and inside-out: Outside-in because of shear stress damage to the blood-brain barrier, but inside-out because of the starvation and hypoxia of the brain due to impaired transfer of nutrients and oxygen due to deranged flow. The initial event, however, remains outside.
Yes. I suppose CCSVI is something in the limit. And you are right. It can be considered inside-out.

And I think that is a very important fact because outside-in similar diseases (NMO and normal EAE) do not present oligoclonal bands, which are typical of MS. The OCBs means that something weird is happening INSIDE the CNS, before the BBB gets broken.

I am quite sure that MS is inside-out. The hypoxia could explain the disregulation of the CNS, or maybe it could be other factor, but all the theories outside-in are derived from EAE and from my point of view are invalid.
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