Study indicates CCSVI does not cause 'MS' in mice

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Study indicates CCSVI does not cause 'MS' in mice

Postby MSUK » Wed Mar 28, 2012 12:03 am

Image

Mice that have their jugular veins ligated to simulate CCSVI do not develop any brain inflammation or demyelination, suggesting yet again that ‘veinous insufficiency’ does not cause multiple sclerosis.

Researchers from Harvard Medical School in the US took 20 mice, ligated both jugular veins and observed them for six months.

Fifteen control mice were given a sham ligation procedure and another eight were induced with experimental autoimmune encephalomyelitis as negative controls.

Despite CT venography confirming the ligation produced hemodynamic changes, MRI demonstrated there were no signs of blood-brain barrier breakdown or neuroinflammation.

In addition, cytometry and histopathology showed ligation didn’t result in any increase in inflammatory cell populations or demyelination.

Moreover, no clinical signs were observed in any of the ligated mice.... Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/2944
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Re: Study indicates CCSVI does not cause 'MS' in mice

Postby Robnl » Wed Mar 28, 2012 12:06 am

They only looked at the jugulars??? There are about 20 veins that can be problematic...
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Re: Study indicates CCSVI does not cause 'MS' in mice

Postby MSUK » Wed Mar 28, 2012 12:41 am

Yes not exactly a representative study by any means,......
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Re: Study indicates CCSVI does not cause 'MS' in mice

Postby Cece » Wed Mar 28, 2012 4:41 am

I wonder if there were differences between their study and Dr. Thanaporn's (other than the negative results here and mild but significant results there)?
chronic-cerebrospinal-venous-insufficiency-ccsvi-f40/topic15635.html

from ISNVD 2011
A murine model of CCSVI is associated with mild but significant impairment of gait as assessed by neurobehavioral testing - P. Thanaporn USA


They were going to test on marmosets next, which have a cerebospinal drainage system similar to humans.

If CCSVI + time = MS, then the mice's lifespan doesn't allow for enough time for the chronic action of CCSVI.
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Re: Study indicates CCSVI does not cause 'MS' in mice

Postby DougL » Wed Mar 28, 2012 5:03 am

my partner also showed no signs of MS after 6 months of having CCSVI.

no signs after a year and even 10 years.

however, sometime around the 20 year mark, she had her first attack of ON.

i am not implying that CCSVI caused her MS progression or even contributed to it. we need to study her to learn that. however, there is no one who can convince me that having CCSVI helped slow down her MS progression.

there are no MS specialist who can tell me how to cure her. there are doctors who tell me they can fix her CCSVI.

so now we wait for 20 years and see if fixing her CCSVI will help her MS. she told me that a few years before she met me, her MS went from RR to a slow steady decline.

in my very unprofessional opinion, as we approach 1 year of me observing her and 6 months post CCSVI, i think her MS progession has either stopped, slowed down dramtically, or reversed a bit. there a many things that contributed to this change - CCSVI surgery only being one.

so why did i say all that. because i wish the groups doing these kinds of studies on mice would spend their dollars on the pwCCSVI. imagine the knowledge we could gain if they would sponsor my partner and other pwCCSVI who have had treatment but are unable to get the followup care and studies with the IR's.

we have a whole lab full of pwCCSVI to study. we don't need mice.
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Re: Study indicates CCSVI does not cause 'MS' in mice

Postby Cece » Wed Mar 28, 2012 9:00 am

It's possible that ligation may cause more congestion but less reflux than a partial blockage. Depending on the hemodynamics. Dr. Tucker was working on equations that could be helpful.
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Re: Study indicates CCSVI does not cause 'MS' in mice

Postby Donnchadh » Wed Mar 28, 2012 11:48 am

Dr. Neuro Oligist's latest reseach paper confirms this finding as well:

chronic-cerebrospinal-venous-insufficiency-ccsvi-f40/topic13644-60.html

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Re: Study indicates CCSVI does not cause 'MS' in mice

Postby Billmeik » Wed Mar 28, 2012 12:59 pm

It's great news that someone tried to replicate Putnam even if the results aren't very good. We used to hypothesize that someone would try it on mice, and the animals wouldn't live long enough

Putnam's dogs took 10 months to develop their encephalomyelitis if I remember. I hope the marmosets live long enough.
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Re: Study indicates CCSVI does not cause 'MS' in mice

Postby drsclafani » Wed Mar 28, 2012 1:27 pm

squiffy2 wrote:Image

Mice that have their jugular veins ligated to simulate CCSVI do not develop any brain inflammation or demyelination, suggesting yet again that ‘veinous insufficiency’ does not cause multiple sclerosis.

Researchers from Harvard Medical School in the US took 20 mice, ligated both jugular veins and observed them for six months.

Fifteen control mice were given a sham ligation procedure and another eight were induced with experimental autoimmune encephalomyelitis as negative controls.

Despite CT venography confirming the ligation produced hemodynamic changes, MRI demonstrated there were no signs of blood-brain barrier breakdown or neuroinflammation.

In addition, cytometry and histopathology showed ligation didn’t result in any increase in inflammatory cell populations or demyelination.

Moreover, no clinical signs were observed in any of the ligated mice.... Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/2944


I concede.
This data is just overwhelming. This evidence gives us reason to pack up and go home.

I am going to throw away all my catheters and use my balloons for my grandson's birthday party.

On the other hand.... it took me two minutes to find out shockingly that the mouse brain IS DIFFERENT FROM THE human brain. NOt to mention that we don't even look like mice (any longer) and we stopped acting like mice sometime around 2007

The cerebral venous drainage of the mouse is not like that of the human. The major vein that drains the mouse intracranial circulation, is the retroglenoid vein that is a continuation of the transverse sinuses. It does not even exist in humans except as a rare anomaly. The internal jugular veins and the vertebral veins are not the major output.

Is this published in a journal? if so, which journal published this. what are the affiliations of the authors? who sponsored this research

read below...

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Re: Study indicates CCSVI does not cause 'MS' in mice

Postby Cece » Wed Mar 28, 2012 1:55 pm

I found the full article: http://www.plosone.org/article/info%3Ad ... ne.0033671

After confirming successful bilateral JV ligation, we investigated whether JVL resulted in altered cerebral hemodynamics. The JVL group demonstrated significantly increased cerebral retention of nuclear perfusion agent, Tc-99m-exametazime, compared to the sham group expressed as the percentage of the injected dose per gram of tissue (%IDGT = 7.09±0.42 (sham) vs. 8.29±0.11 (JVL), p = 0.024, Fig. S1) at 5 months post surgery. These results indicate that bilateral jugular vein ligation altered cerebral hemodynamics in the JVL group. Together with the structural abnormalities seen on CT venograms, these results confirm that we have established a mouse model of chronic cerebral venous insufficiency.
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Re: Study indicates CCSVI does not cause 'MS' in mice

Postby Cece » Wed Mar 28, 2012 2:02 pm

No mention of the retroglenoid vein, but some other possible variables are discussed:
Both posture and activity may therefore potentially play a role in exacerbating the effects of venous congestion resulting from venous stenosis. To address these possible confounding variables, we aimed to maximize the resting state of venous pressure by surgically ligating both JVs in order to create an extreme scenario of increased venous cerebral venous insufficiency. Some studies have reported that 91% of MS patients having either unilateral or bilateral JV stenosis, with 14% exhibiting bilateral stenosis in the jugular veins [6]. In this way, we believe we have accounted for possible differences in cerebral venous hemodynamics between mice and humans by creating a murine model with relatively greater cerebral venous insufficiency than previous positive studies have reported in humans [6]. The mice were followed for up to 6 months after JVL, a considerable part of the lifespan of SJL mice (typically around 400 days) which, particularly given the maximization of venous pressure by bilateral JVL, should be more than sufficient for disease manifestation if there was a relationship between venous congestion and demyelination.
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Re: Study indicates CCSVI does not cause 'MS' in mice

Postby AnCap » Wed Mar 28, 2012 2:22 pm

This isn't really surprising. CCSVI does NOT cause MS...at least not on its own. CSF flow problems will probably be found to be the root cause of MS in conjunction with congenital CCSVI abnormalities, mostly bad valves or missing/underdeveloped veins. Stenoses probably develop later.
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Re: Study indicates CCSVI does not cause 'MS' in mice

Postby Billmeik » Wed Mar 28, 2012 6:57 pm

really I think cattle are the best test subjects. Eat the patient. The long life and higher mammal status are key.The fact that they were going to be killed anyway makes autopsy obvious.
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Re: Study indicates CCSVI does not cause 'MS' in mice

Postby 1eye » Wed Mar 28, 2012 8:00 pm

I think it micght be necessary to have an upright animal which sleeps lying down, and whose outflow changes significantly between the two postures. Sleeping schedule may also be a factor. Some animals sleep nearly all the time.
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Re: Study indicates CCSVI does not cause 'MS' in mice

Postby DougL » Thu Mar 29, 2012 4:35 am

drsclafani wrote:The cerebral venous drainage of the mouse is not like that of the human.


Dr S is there any way to understand the full impact of CCSVI on a human by studying anything but humans?

Based on what i have read about CCSVI, i think it is very likely that we have thousands of kids out there that have some type of bloodflow problems but show no other signs of any other illness such as MS or Lupus. Why can't we study them?

Is it an ethical issue? I don't know what would happen if those kids being studied (but not treated) developed some illness.

Since i have been reading about CCSVI, I have wondered something. Is CCSVI hereditary? If i had CCSVI as many people reading this do, and I had children, would i get them tested and treated even though they show no other signs of illness? This study showed that if i was a mouse, i wouldn't have to worry - yaay!
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