Well, I'm certainly way outside that EAE/MRI box. Too bad I'm not a researcher with some scientific background.
I haven’t had an opportunity to check the new links you gave us, but with such a discussion I wanted to weigh in on the topic. And, despite the fact I have no scientific background, I’m still trying to try make the tiniest bit of sense out of all this MS information.
I think I agree with most of your speculation Finn. It sure is fun to speculate.
I can personally put my own scenario in your speculation and end up with MS as not auto-immune.
Right now I tend to think of MS as a single disease process with lots of variables influencing whether or not one actually gets it, i.e, genetic predisposition with variable penetration that’s heavily dependent on a host of environmental factors (exposure to sun, viruses, bacteria, etc.). Then, cumulative physiological responses to stress
(not psychological)and other hormone shifts finally reach a level and point that allows susceptible brain cells to die, inflammation is ignited and there's now a visible expression of MS as an “inexplicable disease.”
As Harry said though, the real question in my mind now is “what is causing the original damage?” What is prompting the oligodendrocytes to die in the first place?
I’ve already speculated about cortisol. I don’t know if c. pn. in a dormant state would kill oligodendrocytes given the right "stressors". But I have found some information related to the front page article MS Deterioration Reversed with Antibodies and Neuroprotectors (Glypromate/NBQX)
that suggests glutamate can kill oligodendrocytes.
The first is Glutamate excitotoxicity in a model of MS
by Pitt, D et al from the Albert Einstein College of Medicine, NY, Nat Med 2000 (PMID 10613826)
In this report,
NBQX …resulted in substantial amelioration of disease, increased oligodendrocyte survival, had no effect on lesion size and did not reduce the degree of central nervous system inflammation.
The abstract concludes:
Thus, glutamate excitotoxicity seems to be an important mechanism in autoimmune demyelination, and its prevention with AMPA/kainate antagonists may prove to be an effective therapy for MS.
The second is The link between excitotoxic oligodendroglial death and demyelinating diseases
by Matutue, C,, et al from Spain in Trends Neurosci. 2001 (PMID 11250007)
However, acute and chronic alterations in glutamate homeostasis can result in overactivation of AMPA and kainate receptors and subsequent excitotoxic oligodendroglial death. Furthermore, demyelinating lesions caused by excitotoxins can be similar to those observed in MS……indicates that oligodendrocyte excitotoxicity could be involved in the pathogenesis of demyelinating disorders.
Now, I had to look up excitotoxicity
to be sure it meant cell death and it does. Check out http://www.alscenter.org/about_als/excite.cfm
for a discussion of glutamate and cell death. And, what’s great, per the This is MS article, NBQX is already available. So, it seems to me like NBQX could be a “not auto-immune” neuroprotective treatment of sorts for MS based on this and the New Zealand research. I'm hoping
But, Harry's question remains, “What is causing the original damage?” “What is causing the oligodendrocytes to die?" What are some other possibilities for this?
Take care everyone. Enough for now.
(BTW Finn, I tried that URL tag, what a mess
, but I haven't given up on that either! )