This Is MS Multiple Sclerosis Community: Knowledge & Support

Maybe I'm missing something, but I'm surprised that no one (as far as I can tell) has delved into the link between what Dignan has called the two biggest recent developments in MS -- CCSVI and the possibly integral role astrocytes play in the development of MS.

I've only quickly scanned a couple of abstracts, but it seems that there's a lot of research about astrocytes playing a critical role in cerebral blood flow. Could it be possible that the reflux from CCSVI stenoses somehow damages astrocytes and triggers a chain reaction that leads to inflammation and neurodegeneration?

Crabby-
You're right....Astrocytes are very important...they help maintain the endothelial lining of the blood brain barrier- but not to speak for everyone here- I personally feel that they are merely bystanders or victims in the CCSVI process, and we have a better understanding of their place in the chain of events thanks to Dr. Zamboni.

This is the order Dr. Zamboni puts forth in his latest paper on cerebral bloodflow-the abstract and charts are in the research sticky-

1. CCSVI - chronic cerebrospinal venous insufficiency- a cerebral venous outflow abnormality caused by a congenital venous malformation
2. iron deposition into and oxygen deprivation of brain tissue
3. hypoxia and cellular death
4. activation of immune system

I suppose the astrocytes would come into play at step 2, where the bloodbrain barrier is broken due to shear stress. But the astrocytes do not initiate this process....they are affected by the reflux created by stenosis- Step 1.

The ECTRIMS study just looked like another hyperfocusing on one small piece of the puzzle. Zamboni's work provides an over-arching explanation of the process- that's why I was not jumping up and down at the new research (but I do appreciate dig's posting and your mention- because they are obviously related.)
cheer

_________________
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
dual stents placed 5/09
CCSVI in MS

_________________
RRMS Dx'd 2007, first episode 2004. Bilateral stent placement, 3 on left, 1 stent on right, at Stanford August 2009. Watch my operation video: http://www.youtube.com/watch?v=cwc6QlLVtko, Virtually symptom free since, no relap

Just want to add that on the surface it seems the info about astrocytes and MS could be quite consistent with the info on CCSVI.

Per Hollie's (Accelerated Cure Project) 2009 Ectrims notes about Dr. Prineas' Charcot Award Lecture:

It seems possible that ischemia also induces reactive astrocytes. Per this abstract-- Acute astrocyte activation in brain detected by MRI: new insights into T(1) hypointensity


I thought it was interesting anyway...Take care all

Sharon

A slightly off-topic question on this (I was pondering starting a new thread, or posting it in the "skeptics" thread, but since I don't consider myself skeptic this is perhaps the best place for it):

Could you cheer and/or others summarize what the evidence we have for the venous issue being generally congenital? I didn't see this clearly stated in the Zamboni article. There's been some discussion over in the antibiotics forum of the stenosis being caused by ulcers and Cpn involvement, etc.

I can remember two arguments in favor of them being *often* congenital. One is that many patients treated by Dr. Dake had twisted jugulars or jugulars squeezed by surrounding material, like jawbone. Another is Zamboni re-visiting people (as far as I know it is not clear how many) in Sardinia after 20 or so years, who he had diagnosed with (some form of?) venous malformations in their childhood to find that now 90% of them had MS.

Also, an argument against auto-immune involvement in causing the stenosis (but maybe not an argument against them being caused by ulcers caused by an infection) was given at the conference following a detailed analysis of the vein walls (at least that's what I remember, I can't find it anymore).

One thing that puzzles me is that (as I read it) *azygos reflux* is seen more often in secondary progressive patients than in relapsing-remittent ones. *Azygos malformations* on the other side are (as I understand) not seen at all by Dr. Dake. This would mean that at least the azygos reflux is not congenital (except for, maybe, in primary progressive people), and caused by something else.

Radeck-
please refer to the Bologna notes on Marie's 2nd post here at the top of the page:
http://www.thisisms.com/ftopict-7098.html
Dr. Byung B. Lee gave a presentation on congenital truncular venous malformations- associated with the Caucasian race and formed in utero. All of the discussion on the vein walls collagen I and collagen III are there, as well. If you would like to do more research on TVMs and start a new thread, go ahead!

Back to astrocytes....
Sharon- thank you for the study on ischemic changes to astrocytes- makes alot of sense in the CCSVI paradigm.
cheer

_________________
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
dual stents placed 5/09
CCSVI in MS

Due to Cece's info on the two compartment model of cerebral model of blood flow I spotted this thread from Crabby in Sep 2009. For me astrocyctes are critical in the etiology of MS although I am not sure where they fit into the cascade, which leads to MS. For folks who like detail this needs revisiting.
MarkW

_________________
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 10 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html

Putting Zamboni on CCSVI (not iron) and Prineas on Astrocyctes together would be a fascinating discussion. MarkW


Here are Hollie's notes:
Friday September 11, 2009
Plenary Session 2: Charcot Award Lecture
The pathogenesis of relapsing and remitting multiple sclerosis – versions one to five and counting
J. Prineas (Sydney, AU)
Dr. Prineas received this year's Charcot Award for his contributions to understanding the pathology of MS, based in particular on his extensive analysis of MS tissue. In his talk, he divided the historical conception of MS into five phases (actually, he added a sixth new one at the end):
•Charcot's era: MS is a disease of the myelin involving excess glial tissue that compresses and compacts myelin, leaving the axons intact.
•1870-1916: Myelin destruction in MS occurs acutely and begins around blood vessels.
•1950-1960: There are other diseases of the central and peripheral nervous system characterized by perivascular demyelination (such as EAE and Guillain-Barre).
•1960-1985: Myelin destruction in MS and EAE is caused by macrophages; he showed some neat pictures of macrophages squeezing their way into the outer layer of myelin around an axon. Remyelination can occur within a couple of weeks, indicating that the environment is no longer hostile to oligodendrocytes.
•2004: The myelin targeted by macrophages in MS may not be normal myelin -- rather, it displays markers that attract macrophages to destroy it. He has seen lesions with apoptotic ("suicidal") oligos outside the lesion, and myelin breakdown inside the lesion with no oligo cell bodies to be found. Lesions characterized by apoptotic oligos have few lymphocytes. In newly developing lesions, he views three zones: (1) outer zone with some apoptotic cells and activated microglia but no macrophages, (2) a phagocytic zone with macrophages, (3) a post-phagocytic zone with loss of myelin and higher number of T cells and plasma cells than in the other two zones. He does not know why the oligos become apoptotic and whether the activated microglia are a cause or an effect of that.
•He believes that neuromyelitis optica (NMO), which appears to be a disease of astrocytes, is the demyelinating disease that most closely resembles MS. In NMO, there is an even deposition of complement C9 neo along the glial limiting membrane outside the blood vessel, then there is a gathering of macrophages. Astrocytes are destroyed (they may come back but are abnormal), and myelin loss happens after the loss of astrocytes. Apoptotic oligos have been seen in NMO lesions too. In MS, the connection of astrocyte "foot processes" with the glial limiting membrane is often gone (these foot processes form part of the blood-brain barrier and are a prominent target in NMO). He feels that NMO and MS are so alike that they must have something in common -- perhaps MS is also a disease of astrocytes?
* * * * * * * * * * * * * * * *

_________________
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 10 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html

Is this the same order of events in "MS"? In "MS" are astrocytes destroyed or abnormal?
I have seen the term used a lot -- activated microglia. What are they? Good, bad, neither? What activates them?

_________________
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'_MS' is over - if you want it
Patients sans/without patience

Hi one eye---
Astrocytes are back in MS research, with a new paper--I wrote about it yesterday on FB.
Astrocytes are the most abundant cell in the human brain. One of the most important things astrocytes do is support the endothelial cells in our brain, and maintain the very important blood brain barrier. The blood brain barrier should have tight junctions, that don't allow blood particles into brain or spinal tissue. They are not bad guys....they are products of their environment, and they are regulators. They respond to an injurious situation, like hypoxia.

Here's the new paper link:
http://www.jci.org/articles/view/60842

Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease



This is the first study that has noted the importance of astrocyte derived VEGF in the formation of lesions and brain damage in a model of MS.
Please note the other diseases that have VEGF created "vascular permeability"--hypoxia and myocardial infarction. Vascular diseases. VEGF-a is activated in situations where there is low oxygen, and the organ begins to suffer the effects of low O2. Vascular endothelial growth factor (VEGF) is a chemical signal produced by cells that stimulates the growth of new blood vessels. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate.
VEGF's normal function is to create new blood vessels during embryonic development, new blood vessels after injury, and new vessels (collateral circulation) to bypass blocked vessels.

sounds like CCSVI/slowed perfusion/could be linked to this new discovery. More research ahead.
cheer

_________________
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
dual stents placed 5/09
CCSVI in MS

I wish I could say such far reaching things after my research 1eye but these words are from Prof Prineas.

When researchers answer those questions 1eye we will be closer to understanding the causes of MS.
MarkW

_________________
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 10 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html

NMO is different than MS...astrocytes are destroyed in NMO by auto-antibodies. There are no autoantibodies in MS and no astrocyte destruction in MS.
here's the most recent Prineas and Barnett paper on that, from 2012---these researchers have now differentiated astrocytes in NMO and MS---
http://msj.sagepub.com/content/early/20 ... 5.abstract


In MS--astrocytes are a "product of their environment". They are not destroyed, but they are activated to perform a variety of functions in MS. Some are good, some not so helpful. Here's a great paper explaining what they do, one eye.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858316/

The paper I linked above shows how VEGF might be the reason astrocytes are activated in MS. To bring O2 to ischemic tissue, to reroute around blocked blood flow.
cheer

_________________
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
dual stents placed 5/09
CCSVI in MS

Makes sense to me. I wonder about the O2-vein-genesis/VEGF connection. Maybe it's an automatic reaction programmed by DNA, to low O2?

_________________
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'_MS' is over - if you want it
Patients sans/without patience

double post - sorry

How about this study http://www.jneurosci.org/content/32/14/4841.abstract . From what I can grasp FPN (ferroportin) was deleted from astrocytes and it hindered remyelination. This ties in with Genmati's gene study that highlighted the FPN gene in MS. Probably doesn't tie in with CCSVI?