CCSVI, Hypoperfusion and MS

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

Re: CCSVI, Hypoperfusion and MS

Postby Cece » Sun Feb 05, 2012 5:18 pm

Differential matrix metalloproteinase expression in cases of multiple sclerosis and stroke

Multiple sclerosis (MS) and stroke pathology are characterized by blood–brain barrier breakdown, leucocyte emigration, and tissue destruction. Each process is thought to involve the matrix metalloproteinases (MMP), but little is known of their expression. We undertook to investigate whether MMP expression is dependent on the nature of the CNS lesion and whether expression would coincide with the histopathology. MS or cerebral-infarct tissue was examined for the presence of gelatinase-A, gelatinase-B, matrilysin and stromelysin-1. Gelatinases A and B and matrilysin expression was found to be up-regulated in microglia/macrophages within acute MS lesions. In active-chronic MS lesions, matrilysin and gelatinase-A expression was pronounced in the active borders. In chronic MS lesions, the expression of matrilysin was confined to macrophages within perivascular cuffs. The pattern of MMP expression in infarct lesions differed considerably. Gelatinase-B was strongly expressed by neutrophils in tissue from patients up to 1 week after an infarct, whereas gelatinase-A and matrilysin staining was much less marked. From 1 week to 5 years, neutrophils were absent and the large number of macrophages present were expressing matrilysin and gelatinase A. Only a low level of gelatinase-A and matrilysin expression was observed in normal brain controls. Thus, MMPs are expressed in inflammatory lesions in the CNS, but their individual expression is dependent on the nature and chronicity of the lesion. However, the general pattern of expression, in perivascular cuffs and in active lesions, supports a role for these enzymes as mediators of blood–brain barrier breakdown and tissue destruction, both in MS and in cerebral ischaemia.

This is the one orion linked. I don't understand it well enough to say what it means but it's interesting.

1eye, all your attacks were there in the morning? I would be afraid to lie down to sleep. I would agree with you that something postural or jugular was going on.
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Re: CCSVI, Hypoperfusion and MS

Postby Cece » Sun Feb 05, 2012 5:19 pm

Cece wrote:
Differential matrix metalloproteinase expression in cases of multiple sclerosis and stroke

Multiple sclerosis (MS) and stroke pathology are characterized by blood–brain barrier breakdown, leucocyte emigration, and tissue destruction. Each process is thought to involve the matrix metalloproteinases (MMP), but little is known of their expression. We undertook to investigate whether MMP expression is dependent on the nature of the CNS lesion and whether expression would coincide with the histopathology. MS or cerebral-infarct tissue was examined for the presence of gelatinase-A, gelatinase-B, matrilysin and stromelysin-1. Gelatinases A and B and matrilysin expression was found to be up-regulated in microglia/macrophages within acute MS lesions. In active-chronic MS lesions, matrilysin and gelatinase-A expression was pronounced in the active borders. In chronic MS lesions, the expression of matrilysin was confined to macrophages within perivascular cuffs. The pattern of MMP expression in infarct lesions differed considerably. Gelatinase-B was strongly expressed by neutrophils in tissue from patients up to 1 week after an infarct, whereas gelatinase-A and matrilysin staining was much less marked. From 1 week to 5 years, neutrophils were absent and the large number of macrophages present were expressing matrilysin and gelatinase A. Only a low level of gelatinase-A and matrilysin expression was observed in normal brain controls. Thus, MMPs are expressed in inflammatory lesions in the CNS, but their individual expression is dependent on the nature and chronicity of the lesion. However, the general pattern of expression, in perivascular cuffs and in active lesions, supports a role for these enzymes as mediators of blood–brain barrier breakdown and tissue destruction, both in MS and in cerebral ischaemia.

This is the one orion linked. I don't understand it well enough to say what it means but it's interesting.

1eye, all your attacks were there in the morning? I would be afraid to lie down to sleep. I would think too that something postural or jugular was going on.
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Re: CCSVI, Hypoperfusion and MS

Postby cheerleader » Mon Jun 25, 2012 7:24 pm

Hey gang---
For those who might still be interested in the connection to hypoperfusion, CCSVI and MS, I wrote up all of the research and links to back up the theory of MS as a neurodegernerative disease of hypoperfusion created by the collateral circulation of CCSVI-- with relapses, inflammation and immune activation due to periods of reperfusion. This explains the relapsing/remitting nature seen at the beginning of the disease. I think it covers all of the research, but please, if you're on Facebook, make some comments and help me figure out the missing pieces.
Thanks!!
cheer
https://www.facebook.com/notes/ccsvi-in ... 0894457211
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Re: CCSVI, Hypoperfusion and MS

Postby 1eye » Mon Jun 25, 2012 8:02 pm

If there were a lot of macrophages around, maybe it was to engulf venous blood cells that had leaked across the barrier. Would that make the leakage self-perpetuating because they expressed MMP, or is it just a side-benefit?
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'MS' is over - if you want it
Patients sans/without patience
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Re: CCSVI, Hypoperfusion and MS

Postby cheerleader » Mon Jun 25, 2012 9:13 pm

Good point, one eye, macrophages do show up in reperfusion--from ischemic injury and due to microhemorrhage (leaking of red blood cells)--one of the events that happens in reperfusion injury due to venous hypertension. Microhemorrhage happens above the blockage. That would also call in MMPs. It's a bit of a vicious cycle, as the blood brain barrier becomes weakened from various factors.

I have a paper linked in the note that discusses venous reperfusion injury and how it is related. It's amazing to see how much reperfusion injury looks like an MS relapse, when you go thru all the common elements. The immune reaction, opening of the BBB, and demyelination are the ones that blew me away....
And Dr. Dake's comment at ISNVD about perfusion injury (hyperperfusion) happening before an MS lesion forms was the link that helped me put it together. Here's the paper Dr. Dake was talking about.
Changes in Cerebral Perfusion precede plaque formation in MS
http://brain.oxfordjournals.org/content ... 1.full.pdf

cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Re: CCSVI, Hypoperfusion and MS

Postby Cece » Mon Jun 25, 2012 10:05 pm

chronic-cerebrospinal-venous-insufficiency-ccsvi-f40/topic16872.html#p167661

Cece wrote:We have not talked much about reperfusion injury but it must be a part of the cycle with MS. Here's the wikipedia on it:
Reperfusion injury refers to tissue damage caused when blood supply returns to the tissue after a period of ischemia. The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and oxidative damage through the induction of oxidative stress rather than restoration of normal function.

Presumably in CCSVI, it is low-grade oxgyen deprivation, not total ischemia, although there would also seem to be trigger events where oxygen levels are stressed (perhaps childbirth, perhaps time spent at high altitudes).

I also think about my own procedure and the dramatic brightening of colors afterwards. The assumption is that the brightening was due to a restoration of normal brain oxygen levels.

So are we at risk of reperfusion injury, either in the normal course of our MS/CCSVI or immediately after the procedure, if the degree of oxygen deprivation was relatively severe?

We have known a few patients who have gotten worse immediately after what seemed to be a successful procedure in terms of no clotting and the blood flowing properly. We haven't had a good answer for that. It's only been a few cases.
The damage of reperfusion injury is due in part to the inflammatory response of damaged tissues. White blood cells, carried to the area by the newly returning blood, release a host of inflammatory factors such as interleukins as well as free radicals in response to tissue damage.[1] The restored blood flow reintroduces oxygen within cells that damages cellular proteins, DNA, and the plasma membrane. Damage to the cell's membrane may in turn cause the release of more free radicals. Such reactive species may also act indirectly in redox signaling to turn on apoptosis. Leukocytes may also build up in small capillaries, obstructing them and leading to more ischemia.

Reperfusion injury may be the name for what we've been experiencing all along, when we talk about the white blood cells attacking. Steroids or DMDs would be effective against this. It can be an excessive reaction to the injury, so that as much or more damage is done by the white blood cells' attack as it was by the initial oxygen-deprivation injury.

Cheer has been saying all along that MS may be more comparable to a series of ischaemic events.

As for if reperfusion injury might occur (particularly in more easily inflamed brains?) as an immediate result of CCSVI treatment, I don't know. Hypothermia and hydrogen sulfide are the only things listed in wikipedia as protective against reperfusion injury. Presumably most of us have low grade chronic issues rather than acute, but we also have areas of CNS damage that might be particularly vulnerable to another insult.

Those are my thoughts from before on reperfusion injury in CCSVI.
I read through your facebook note. Much agreement. None of this is proven but it is a respectable theory that warrants investigation. The addition I'd make is the possibility of reperfusion injury immediately after CCSVI treatment in some patients.

My own relapses have occurred infrequently and are associated with an event such as childbirth, physical exertion at high altitudes, etc. Reperfusion injury offers an explanation in my disease course. Prior to CCSVI theory, there were no good explanations. I am grateful for how far we've come, and how much more can yet be done.
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Perfusion and MS

Postby MarkW » Tue Jun 26, 2012 12:34 pm

cheerleader wrote:...... Here's the paper Dr. Dake was talking about.
Changes in Cerebral Perfusion precede plaque formation in MS
http://brain.oxfordjournals.org/content ... 1.full.pdf
cheer

Interesting paper Cheer. It is from 2003 and no one followed up on the research in nearly a decade! It is amazing how close minded the neuros have been to research from other neuros which deviates from the immune model of MS. I do not feel that the paper explains what is happening in MS but it certainly gives avenues for future research.
Kind regards,
MarkW
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 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
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