Research: Animal Studies Suggest that CCSVI is a Non-Starter for MS


An alternative hypothesis has been proposed implicating chronic cerebrospinal venous insufficiency (CCSVI) as a potential cause of multiple sclerosis (MS). We aimed to evaluate the validity of this hypothesis in a controlled animal model. Animal experiments were approved by the institutional animal care committee. The jugular veins in SJL mice were ligated bilaterally (n = 20), and the mice were observed for up to six months after ligation. Sham-operated mice (n = 15) and mice induced with experimental autoimmune encephalomyelitis (n = 8) were used as negative and positive controls, respectively. The animals were evaluated using CT venography and exametazime to assess for structural and haemodynamic changes. Imaging was performed to evaluate for signs of blood-brain barrier (BBB) breakdown and neuroinflammation. Flow cytometry and histopathology were performed to assess inflammatory cell populations and demyelination. There were both structural changes (stenosis, collaterals) in the jugular venous drainage and ahemodynamic disturbances in the brain on exametazime scintigraphy (p = 0.024). In the JVL mice, gadolinium MRI and immunofluorescence imaging for barrier molecules did not reveal evidence of BBB breakdown (p = 0.58). Myeloperoxidase, matrix metalloproteinase, and protease molecular imaging did not reveal signs of increased neuroinflammation (all p>0.05). Flow cytometry and histopathology also did not reveal increase in inflammatory cell infiltration or population shifts. No evidence of demyelination was found, and the mice remained without clinical signs. Despite the structural and haemodynamic changes, we did not identify changes in the BBB permeability, neuroinflammation, demyelination, or clinical signs in the JVL group compared to the sham group. Therefore, our murine (IT IS MOUSE!!!!!!! NOT MURINE THIS CAN MEAN RAT!!!!!-BOTH FROM THE GENUS MURIDAE…….YOU DON’T GET RATINE) model does not support CCSVI as a cause of demyelinating diseases such as multiple sclerosis.

I told you this was going to happen!!!! Ugh………what’s more this is no doubt the first one of more to follow. 

Well it is official….. blocked jugular veins do not give you MS!!!!, because animals studies show this. You shout they did not not use the Zamboni ultrasound method to detect blockage!, but you can not get much more blocked than having the veins tied shut!. Where there any Dawsons fingers?…..Apparently Not!. Importantly there was no demyelination and no oligodendrocyte death before inflammation, because there was no inflammation!!
However, they could find inflammation and evidence of blood brain barrier disturbances in autoimmuniy, where you could see inflammation and demyelination.
So you put the idea that blocked veins cause, demyelinating disease forward………..and the hypothesis fails. The hypothesis has problems not because it fails in animals, but because it does not take into account the genetics and the aetiology of MS as well as treatment effects and other current knowledge of MS, but I do hope I am wrong and the trials are positive, just as I want all potential drugs to work.

Could this be wrong…..of course it could.

So you say animals do not get MS….well apparently not when they have blocked neck veins!!

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  • CCSVI is much more than 2 blocked jugulars. The model is simplistic as it doesn't recreate the necessary blood flow reversals. The researchers say they waited for six months, but is that time enough? I just wonder how would mice describe the hemodynamic changes in their heads: as headaches? as fatigue?

    Let alone differences between species.

    But i find it interesting that people who have undergone the CCSVI treatment know they have restenosed by the return of their symptoms.

  • Yes that would be a good study to to do if the effect is short lived based on reports from the New York Group, when symptoms return is there a re block is there a re block if symptoms don't return. Again it needs to be done systematically and blinded

  • Is six months enough but if the effect of ccsvi lasts for three months before symptoms reappear why is six months not enough time. A quarter of a lifespan for a mouse.

  • Re "Is six months enough but if the effect of ccsvi lasts for three months before symptoms reappear why is six months not enough time."

    Some reasons as a starter:
    1. The mouse brain is healthy, the MSer's is not.
    2. No reflux in the mouse model.
    3. CCSVI is about abnormal valves, not blockages.

    If we want to go deeper we must find out some other things like:
    1. What's the blood pressure limits in mice?
    2. What's the maximum pressure the BBB in mice can handle?
    3. What's the capacity of the epidural veins?
    4. How does CSF circulate, and what's its proportion to blood volume and scull volume (in mice).
    5. How strong can a reflux become in mice?

  • Mouse brain is healthy, MSers (I think we do not want the apostrophe but you have 2 days left to vote so please vote) is not. Surely it was healthy at some stage or are you born with blockage? If you are it then takes
    years, upto 60 or so, to develop if you are right.

    How do you know no reflux? The blood has to go somewhere and if the vessel is tied it cannot move onwwards?

    Abnormal values not blockages, that is not the way it is portrayed by many including Prof Z. check out the video

    What is the answer to (1-5) in humans, if you cannnot give the answer why ask it of mice? Maybe 4 is easy

  • When I was a kid and asking too many questions, my Dad used to say

    "Give your a**e (A*s=american) a chance!"

    I've been farting ever since.

  • Re "A quarter of a lifespan for a mouse."

    Blood flow is more mechanical than biological process. What seems to count more is the heart rate of the animal compared to that of humans. As i found out, mice have a heart rate of 480-600. That means that 6 mouse months with ligated jugulars equals 60 human months = 5 years. I am not sure that 5 years of blood stagnation is capable of producing enough damage.

    When i say reflux i mean reflux from thorax through the jugulars valves. The mouse model has nothing like that.

  • The lifespan of a mouse is 2 years, tops so 6 months ligation coerrelates to 20 years approx human lifespan. End of. You're getting desperate VV.

  • 6 months how bout u tye them up for 20 yrs considering that is about how long it takes for it to affect brains in humans……this test is garbage and cannot b compared in humans I do not believe this…open ur eyes

  • My eyes are open are yours?.

    They aimed to test a hypothesis and it is what it is…so believe it.

    However you do not have to believe it is the same as human disease, I would probably agree..however concerning 20 years….how do you explain MS in a 2 year old?

    More posts of CCSVI and paediatric MS to come on saturday

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