Joan's great evaluation of the new paper on oxidative damage in MS and how this may be of interest to MS patients was really wonderful. the paper is by Haider et al 2011 and titled "Oxidative damage in multiple sclerosis lesions." See her evaluation here.
Joan's review (includes link to Haider et al 2011)
http://www.facebook.com/note.php?note_id=10150211799777211&comments
Joan has asked me to tie this work in to other research of interest.
As Joan points out, the most interesting aspect of this paper to us is that it suggests that oxidative damage is the key to development of lesions in the MS brain and this could be the initial event. One important thing they noted is that MS lesions generally have a lot of immune system cells in them whereas white matter lesions caused by low oxygen don't have similar immune cell activity. However, they noticed that in the MS patients it was the older lesion areas that had these immune system cells wheras the the newly expanding edge of the lesion didn't have these immune cells.
This suggests that the immune cells came in after the fact and the sequence of events could be:
1. (an unknown factor)
2. triggering oxidative damage to the oligodendrocytes, myelin, and axons
3. microglial (the immune cell that lives in the brain) activation and cleanup of damaged cells
4. recruitment of peripheral immune system cells- Tcells, B-cells inflammatory factors
5. inflammatory immune cells become abundant in lesions where previously damaged
In 2004 Barnett and Prineas revealed goundbreaking research titled "Pathology of a newly forming lesion" in which they identified a similar sequence of events.
The story of Barnett and Prineas research is interesting--they had autopsy samples from a young woman who died only hours after an attack of MS and thus had an unusual chance to see a brand new lesion. They discovered to their surprise that her oligodendocytes had died and the immune system was just barely beginning to activate to send in immune cells to clean up. Prior to this research, everyone thought that T-cells were causing the MS lesion. This was the first time anyone had noted oligodendrocytes dead before these immune cells arrived.
They noted that this phase of the lesion would only last a few hours before the immune cells would arrive to aid cleanup and they speculated that this was why this phase of lesion development was not noticed before.
Dr Barnett and Dr Prineas have worked with other researchers over several later studies affirming that the initial event in an MS lesion appears to be this loss of oligodendrocytes followed by immune system activation. They are still trying to identify the "unknown factor" that causes the damage to the oligodendrocyte, but they believe the damage appears to be similar to what happens when tissue has low oxygen damage.
Another paper by Merik et al 2007 is titled "Lesion genesis in a subset of patients with multiple sclerosis: a role for innate immunity." In this paper the researchers affirm that MS lesions occur against a background of inflammation but it is unknown whether the inflammatory immune system activity is the first event.
Here's a quote "Macrophages and activated microglia are adherent to partly damaged myelin sheaths and axons, suggesting a major role of these cells in the destructive process. Whether such inflammatory lesions are the initial event in tissue injury is, however, currently uncertain." (emphasis mine-notice this is the scientifically correct position, they don't know if the immune system caused the lesion or came in later.)
In their conclusions they note that type III lesions seem to start with some kind of oxidative injury followed by immune system activity and that this appears to be similar to low oxygen states.
Naturally this line of thinking is of interest to CCSVI proponents because it might be interpreted as supporting the hypothesis of venous insufficiency as the initial event in MS because venous insufficiency would cause poor oxygenation and oxidative damage to brain cells.
It also is of interest because in venous disease the immune system comes in too aggressively after the initial venous problem and causes even more damage. It isn't just that there is low oxygen and oxidative damage to cells in venous insufficiency; it's that afterwards the immune system goes nuts trying to clean up. These papers seem to suggest a similar sequence of events in MS.
While it is exciting to see MS research developing along new lines, we do have to be cautious in interpreting these papers for these reasons:
First, while it is possible that oxidative damage is the trigger for oligodendrocyte damage there could be other explanations as well. Dr Prineas has mentioned the alternative possibility that perhaps T-cells in the area of the vein might somehow cause standby damage to the oligodendrocyte. In this idea, the T-cells don't directly damage the oligo but instead are the cause of oxidation, which starts the cascade. The Merik et al paper mentions this possibility too.
Second,the Merik et al paper focused primarily on one type of MS lesion, type III. This could be true of this subset of MS patients and not all MS patients. The Haider et al paper also did most of their work on type III lesions. Type III lesions appear to be similar to lesions caused by low oxygen states. Not all lesions are of this type, though there is some scientific uncertainty about what exactly these lesion types mean. Is it possible that only type III is associated with CCSVI? we are a long way from any such research.
Scientists are characteristically cautious and try to never overstate their findings or "over-reach" for their interpretation when deciding what their findings mean. This is good! We want them to be cautious. I am just grateful that today there is this new line of evaluation that appears to lead away from the old "It was the T-cell that did it" story, because that story is wearing a bit thin and it doesn't seem to be panning out---even if a person's immune system is very well suppressed, MS still progresses. That is not good enough. We need new ideas!
In my CCSVI book (published by the reference division of McFarland) I talk about the lesion project research as well as the Barnett and Prineas work and how all this may tie in to CCSVI. I also have an entire chapter on the immune system and how it functions that can serve as a reference when looking at research like this so it is easier to understand If you'd like a copy go to ccsvibook.com or Amazon and look for "CCSVI as the Cause of Multiple sclerosis: The Science behind the Controversial Theory."
www.ccsvibook.com
The book was recently produced in the digital Kindle format for only 9.99 on Amazon. If a person doesn't have a Kindle they can download the free app for their computer and read the book on there!
http://www.amazon.com/CCSVI-Cause-Multiple-Sclerosis-ebook/dp/B004Z16OU0/ref=sr_1_1?ie=UTF8&m=AG56TWVU5XWC2&s=digital-text&qid=1308020989&sr=1-1
~Marie