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mouse models for CVI

Posted: Sun Jul 04, 2010 8:02 pm
by Cece
In the hopes that someone will replicate Putnam, I looked into if anyone has done a mouse model for chronic venous insufficiency, the condition most similar to chronic cerebrospinal venous insufficiency.

Yes, they have.

http://www.jvascsurg.org/article/S0741- ... 9/abstract
At least three types of animal model were identified that have contributed to a better understanding of the trigger mechanisms and role of inflammatory processes in chronic venous disease. These models involve venous hypertension induced either by acute venular occlusion, placement of a chronic arteriovenous fistula, or ligation of several large veins. Model results suggest that elevated venous pressure and altered flow can trigger inflammatory cascades in the vein wall and venous valves which can cause progressive valvular incompetence and eventual valvular destruction, and which are also important in the skin changes associated with venous disease. Treatment with agents that reduce oxidative stress by scavenging free radicals and that inhibit the inflammatory cascade can prevent the progressive deterioration of function in valves exposed to elevated venous pressure and can prevent the development of reflux blood flow.

Re: mouse models for CVI

Posted: Mon Jul 05, 2010 2:54 am
by frodo
Cece wrote:In the hopes that someone will replicate Putnam, I looked into if anyone has done a mouse model for chronic venous insufficiency, the condition most similar to chronic cerebrospinal venous insufficiency.

Yes, they have.

http://www.jvascsurg.org/article/S0741- ... 9/abstract
At least three types of animal model were identified that have contributed to a better understanding of the trigger mechanisms and role of inflammatory processes in chronic venous disease. These models involve venous hypertension induced either by acute venular occlusion, placement of a chronic arteriovenous fistula, or ligation of several large veins. Model results suggest that elevated venous pressure and altered flow can trigger inflammatory cascades in the vein wall and venous valves which can cause progressive valvular incompetence and eventual valvular destruction, and which are also important in the skin changes associated with venous disease. Treatment with agents that reduce oxidative stress by scavenging free radicals and that inhibit the inflammatory cascade can prevent the progressive deterioration of function in valves exposed to elevated venous pressure and can prevent the development of reflux blood flow.
Wow. It seems that the model did not involve the brain, but the relationship with "inflammatory cascades" and treatment with "free radicals scavenging" is really impressive.

By the way, the link is not clickable. Try to add http:// at the beginning

Posted: Mon Jul 05, 2010 10:12 am
by Cece
Link is still broken! I tried.

Would the inflammatory cascades and free radicals scavenging happens in the same way in CCSVI? This is inflammation within the veins.

One of the differences between CVI and CCSVI (besides proximity to delicate brain and spine tissue!) is the effects of gravity on a condition at the bottom of the body, where blood needs to be pumped up a good distance, and at the top of the body, where gravity is working with us. (We would all be in even worse shape if our brains were in our feet. :) ) Not sure how this affects any comparisons.

This article also talked about in CVI how one blockage causes blocked up blood which causes a further-up valve to blowout...I raised this question in DrS's thread and he did not think much of this was going on in CCSVI, that the valve issues in question are predominantly valvular malformations not secondary blowouts.

The main thing I took away from this article is that making a mouse model is easy enough for CVI. They can occlude the veins or ligate them or whatever the third way was. I don't see doing this in a brain-draining vein as being that different. The difficulty would be in creating the right degree of occlusion, so that a longer-term effect can be seen; MS takes on average 30 years to show up. The other concern might be the structure of the neck and if that affects brain drainage in a mouse as compared to a human. I will look and see if there are mouse models for cerebral thrombosis or that sort of thing can tell us anything.

Posted: Mon Jul 05, 2010 2:37 pm
by AlmostClever
Cece wrote:
MS takes on average 30 years to show up. The other concern might be the structure of the neck and if that affects brain drainage in a mouse as compared to a human. I will look and see if there are mouse models for cerebral thrombosis or that sort of thing can tell us anything.
I was thinking about the lifespan of mice and found that they average 2 years in the lab.

Not very good for a disease that might take 30 years to show itself... how would we speed up the disease progression in mice?

Is this why Putnam used dogs?

Posted: Mon Jul 05, 2010 2:38 pm
by frodo
Well. Keep us informed if you find something!!
About the link, try to remove the URL tags. It should work anyway, but just in case.
If not, the link is here, just to make things easier

http://www.jvascsurg.org/article/PIIS07 ... 9/abstract

Posted: Mon Jul 05, 2010 5:19 pm
by Cece
AlmostClever wrote:I was thinking about the lifespan of mice and found that they average 2 years in the lab.

Not very good for a disease that might take 30 years to show itself... how would we speed up the disease progression in mice?

Is this why Putnam used dogs?
Putnam's dogs showed lesions in nine months, didn't they?

I suppose it doesn't have to be perfect: EAE is by no means a perfect MS autoimmune mouse model, yet it sufficed.

There's got to be someone working on this, wouldn't you think? Or is it that IRs are the ones taking up the cause and IRs don't do mouse research?

(frodo, thanks for the help with the link.)

Posted: Tue Jul 06, 2010 1:45 am
by CureOrBust
Cece wrote:There's got to be someone working on this, wouldn't you think? Or is it that IRs are the ones taking up the cause and IRs don't do mouse research?
I though Stanford was looking into this :?

http://www.thisisms.com/ftopicp-82755.html#82755