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Been reading a lot of cellular level studies the last few days, came across this article and was curious if anyone else has read it or has access to the full thing.

http://www.ncbi.nlm.nih.gov/pubmed/8776576

So, we know that CCSVI alters CSF pathology (according to Zamboni), which is supposedly leading to extravasation of red blood cells due chronic venous insufficiency of the main outflow veins draining the CNS. The effects of this extravasation in the CNS need to be studied but from Chronic Venous Disease in other areas of the body, combined with the evidence of Fibrin Cuffs in CCSVI point to potential iron overload.

Lets jump the fence and talk MS for a second. In MS we know that nerve cells are losing myelin, and the oligodendrocytes that create myelin are dying. I find it interesting that oligodendrocytes are the most iron-laden cells in the CNS, as the iron is necessary for the myelin creating process. I also find it interesting that groups of these oligodendrocytes also group up in the white matter of the brain around veins.....just like MS lesions.

So, if these particular veins are the genesis of the MS lesion, what could the process be? CCSVI causes, over time, endotheleal cell damage through venous hypertension, which in turn cause an iron overload similar to other Chronic Venous Disease. Does it just so happen that this particular area where the BBB damage and iron build-up occurs is the same area of the brain that contains the iron-laden oligodendrocytes?

Interestingly, endotheleal cells and macrophages both create a cytokine called TNFa, Tumor Necrosis Factor alpha, which is a known trigger of oligodendrocyte apoptosis (programmed cell death). Abnormal TNF production is a common factor in many autoimmune diseases. Could it be that the body, in an effort to mediate iron deposition in those areas, is sending necessary things to start the caspase cascading process in oligodendrocyte cells because they are so full of iron?....TNF has been found in MS lesions.

I've been cramming on this stuff for days now, its like the answer is right on the tip of our tongues but we just can't spit it out yet.

I think I read TNF is associated with exacerbations too. So is gamma interferon, so I think.

I also find it interesting that groups of these oligodendrocytes also group up in the white matter of the brain around veins.....just like MS lesions.

are you sure that ism't dead oligos that are around lesion veins. Hypoxia is killing them, causing the inflammation that causes the ms.

Just a theory.

Billmeik wrote: are you sure that ism't dead oligos that are around lesion veins. Hypoxia is killing them, causing the inflammation that causes the ms.

Just a theory.

Here is a quote from the abstract in the linked article:

"Oligodendrocytes are the predominant iron-containing cells in the brain. Iron-containing oligodendrocytes are found near neuronal cell bodies, along blood vessels, and are particularly abundant within white matter tracts. Iron-positive cells in white matter are present from birth and eventually reside in defined patches of cells in the adult. These patches of iron-containing cells typically have a blood vessel in their center"

This was new info for me when I read it.

That's always been a twirler for me, do the dead oligos leave their iron behind, or is the reflux-associated iron killing off the oligos, or a mix of both, leading to the iron deposits noted on the swi scans. Greater minds than mine that's for sure...


Mark

Hello Johnnymac,
Looks like you have outlined about 10+ years of research before we get any definitive answers. I suspect that the key to this research will be replacing the current mouse model of MS with a dog/pig model which includes CCSVI. Interesting thoughts, just do not hold your breath, waiting for an answer.
Kind regards,
MarkW

http://www.thisisms.com/ftopict-10505.html


here's a link where I trot out some of the papers showing people dieing right after an ms attack and a quick autopsy is done. The find dead oligos and no sign of an auto immune attack.

Now are the dead oligos from oxygen depletion or is iron part of it. ?

Dunno. In that thread me and cheerleader agreeed it was oxygen. The iron seems unnecessary.

of course what you are saying is the iron builds up in the oligos..does it kill them?

Marc "Wheelchair Kamikaze" wrote in a post (sorry, can't find it..) about meeting with some Pharma reps (i think) and discussing this very point.

This was one of the rep's ideas about explaining the iron.

I brought this to my neuros attention and asked her opinion - dumb,dumd,dumb - but it makes sense to me!

MarkW wrote:Hello Johnnymac,
Looks like you have outlined about 10+ years of research before we get any definitive answers. I suspect that the key to this research will be replacing the current mouse model of MS with a dog/pig model which includes CCSVI. Interesting thoughts, just do not hold your breath, waiting for an answer.
Kind regards,
MarkW

Yes, there definitely needs to be a new model to test these CCSVI-MS links and theories. However, I did read in one study over the weekend that mice who were iron deficient either did not develop EAE, or developed a more mild form of it. Other articles suggested that iron deficiency is more effective than the current DMDs, at least when it comes to EAE.

http://jn.nutrition.org/cgi/content/full/133/8/2635

Not sure what can be extrapolated from that considering there is no CCSVI in this picture, but perhaps a body that is already low on iron, will not initiate the Oligodendrocyte Apoptosis process because its trying to actively protect any sources of iron in the body? If a person adds iron overload via CCSVI could the body in effect be 'carpet bombing' that particular area to dispose of any and all sources of iron?


Another interesting read on the role of TNF in Oligodendrocyte Apoptosis.

http://ajp.amjpathol.org/cgi/content/full/153/3/801

Johnny,

I am impressed! I wish I understood it all better, but am going to try. I don't think it matters that the research is far off or that it will be a long time coming. What's most fascinating to me is how we are now able to incorporate another paradigm into the one we had, by including the vascular theory, adding an entirely new dimension!
Thank you for all your hard 'reading' work you're doing to bring to us great questions.
By the way, I did see your wife's photographs and they are wonderful. I hope she is able to pursue photography as an art and not as a business, she has a great eye.
Don't want to change the thread topic but I lost sight of the other.

Again, thanks for your research.

Z

Billmeik wrote:
Dunno. In that thread me and cheerleader agreeed it was oxygen.

In my researching I've found numerous references to ROS, this one in particular really caught my eye.

http://brain.oxfordjournals.org/cgi/con ... 28/11/2675

It states that TNF induced Oligodendrocyte Apoptosis is dependent on Apoptosis Inducing Factors (AIF), and are NOT dependent on the Caspase Cascading process to break the cell down and kill it. It goes on to identify ROS, or Reactive Oxygen Species, as an AIF.

I absolutely agree that Oxygen, perhaps ROS, is one of the puzzle pieces.

If you want a copy of the paper contact info@direct-ms.org

but the apoptosis isnt needed if the cell death is caused by hypoxia. I've been a believer in tha apoptosis of oligos in ms for almost 10 years. Now I don't see why cellular suicide is needed. Hypoxia.

bump this is the good stuff

Billmeik wrote:but the apoptosis isnt needed if the cell death is caused by hypoxia. I've been a believer in tha apoptosis of oligos in ms for almost 10 years. Now I don't see why cellular suicide is needed. Hypoxia.

Ah yes, here is study on this very thing:
http://www.ncbi.nlm.nih.gov/pubmed/12559509

More and more its looking like CCSVI is a vehicle of multiple mechanisms, and perhaps symptomatic pathology could be related to these different mechanisms.

CCSVI>Venous Hypertension>Extravasation of Red Blood Cells>Iron Deposition>Cell Death>MS

CCSVI>Venous Hypertension>Hypoxia>Cell Death>MS

Talk about an over-oversimplification, but I do wonder if perhaps CCSVI is presenting multiple mechanisms to Cell Death/MS and that this could make it even more difficult to prove.