A must read article (hypoperfusion stress)...

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

A must read article (hypoperfusion stress)...

Postby orion98665 » Tue Jul 30, 2013 7:27 pm

Oligodendrocyte precursor cells (OPCs) are thought to maintain homeostasis and contribute to long-term repair in adult white matter; however, their roles in the acute phase after brain injury remain unclear. Mice that were subjected to prolonged cerebral hypoperfusion stress developed white matter demyelination over time. Prior to demyelination, we detected increased MMP9 expression, blood-brain barrier (BBB) leakage, and neutrophil infiltration in damaged white matter. Notably, at this early stage, OPCs made up the majority of MMP9-expressing cells. The standard MMP inhibitor GM6001 reduced the early BBB leakage and neutrophil infiltration, indicating that OPC-derived MMP9 induced early BBB disruption after white matter injury. Cell-culture experiments confirmed that OPCs secreted MMP9 under pathological conditions, and conditioned medium prepared from the stressed OPCs weakened endothelial barrier tightness in vitro. Our study reveals that OPCs can rapidly respond to white matter injury and produce MMP9 that disrupts the BBB, indicating that OPCs may mediate injury in white matter under disease conditions.


http://www.jci.org/articles/view/65863
or this
http://www.ncbi.nlm.nih.gov/pubmed/15472111

Isn't it interesting lots of this new research is coming out and published after Dr. Zamboni's findings..???


Bob
orion98665
Family Elder
 
Posts: 135
Joined: Sat May 29, 2010 2:00 pm
Location: Vancouver, Wa

Advertisement

Re: A must read article (hypoperfusion stress)...

Postby 1eye » Wed Jul 31, 2013 9:29 am

White matter lesions from chronic hypoperfusion? Who woulda thunk it?

But this was another mousie study...
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'MS' is over - if you want it
Patients sans/without patience
User avatar
1eye
Family Elder
 
Posts: 2997
Joined: Wed Mar 17, 2010 3:00 pm
Location: Kanata, Ontario, Canada

Re: A must read article (hypoperfusion stress)...

Postby cheerleader » Wed Jul 31, 2013 8:09 pm

Hi Bob--
we'll be hearing more about hypoperfusion, reduced cerebral bloodflow and MS....and you're right. It's not a coincidence. Here's a study conducted on pwMS by one of the researchers selected by the NMSS to look at CCSVI--Dr. Wolinsky. While he didn't find CCSVI --his team has just published this study.

BACKGROUND:
Longitudinal magnetic resonance imaging (MRI) studies show that a fraction of the multiple sclerosis (MS) T2-lesions contain T1-hypointense components that may persist to represent severe, irreversible tissue damage. It is not known why certain lesions convert to persistent T1-hypointense lesions.
OBJECTIVE:
We hypothesized that the T1-hypointense lesions disproportionately distribute in the more hypoperfused areas of the brain. Here we investigated the association between hypoperfusion and T1-hypointense lesion distributions.
METHODS:
MRI and cerebral blood flow (CBF) data were acquired on 45 multiple sclerosis (MS) patients and 20 healthy controls. CBF maps were generated using pseudo-continuous arterial spin labeling technique. The lesion probability distribution maps were superimposed on the CBF maps.
RESULTS:
Two distinct CBF clusters were observed in the white matter (WM) both in healthy controls and MS patients. An overall reduction in CBF was observed in MS patients compared to healthy controls. The majority of the T1-hypointense lesions were concentrated almost exclusively in the WM regions with lower CBF. The T2-hyperintense lesions were more generally distributed in both higher and lower perfused WM.
CONCLUSION:
This study suggests an association between hypoperfusion and T1-hypointense lesions.

http://www.ncbi.nlm.nih.gov/pubmed/23836878

cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
User avatar
cheerleader
Family Elder
 
Posts: 5092
Joined: Mon Sep 10, 2007 2:00 pm
Location: southern California

Re: A must read article (hypoperfusion stress)...

Postby 1eye » Fri Aug 02, 2013 8:54 am

OK, let's get this straight.

hyper = more or stronger than usual (like white spots on a darker background).

hypo = less or weaker than usual (like dark spots on a lighter background).

Everyone who ever had an MRI with "MS" is probably familiar with white spots because they are the ones used to diagnose it. I didn't realize (until after the CTV Zamboni appearance in 2009) what it was (a pattern of the roots of venules), only that my radiologist recognized the pattern as "consistent with a diagnosis of MS".

I don't know of anyone (there may be many) who has seen their "T1-hypointense" spots. They are usually called "black holes". I have seen mine. They are smaller, rounder, and there are many more if them. My brain looks like it was been sprayed with little drops of black paint. Very regular and well separated, no two touching each other. But far more numerous than the white spots.

I thought they were associated with progression and disability. That's why I was astonished to read that the first drug said to treat these spots is another "RRMS"-only drug.

What this paper is saying is that black holes are associated with low blood flow and hypoperfusion (low blood flow in capillaries through from arterial to venous) in brains of pw"MS".

That, I believe, is "consistent with" a venous stenosis in brain outflow (i.e. CCSVI).
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'MS' is over - if you want it
Patients sans/without patience
User avatar
1eye
Family Elder
 
Posts: 2997
Joined: Wed Mar 17, 2010 3:00 pm
Location: Kanata, Ontario, Canada

Re: A must read article (hypoperfusion stress)...

Postby cheerleader » Fri Aug 02, 2013 1:55 pm

Great points, 1eye...the study I linked is looking at hypointense lesions, or "black holes." And one would think that hypoperfusion creating hypointense lesions could be correlated to restricted blood flow. However, we are dealing with neurologists. Wolinsky, in particular--Texan author of the most recent anti-CCSVI studies. And neurologists are fiercely maintaining that it is the mysterious "MS disease process" which is causing tissue loss and demyelination and therefore, the MS brain needs less perfusion. MS causes hypoperfusion, 'cause less tissue needs less blood flow. It's the age old chicken and egg.

Dr. Juurlink addresses this argument in his INCREDIBLE paper The Evidence for Hypoperfusion as a factor in MS Lesion Development. He gives an "it's possible" to the neurological argument. This paper is a must-read.
http://www.hindawi.com/journals/msi/2013/598093/

Saindane and colleagues in an MRI study of remitting-relapsing MS patients and control subjects conclude, based on the correlation between decreased white matter perfusion and decreased mean diffusivity with no changes in fractional anisotropy (indicative of no structural changes), that reduced NAWM blood flow is a primary event and not due to decreased tissue metabolism [38]. It is possible, however, that functional impairments of astrocyte-mediated regulation of blood flow need not necessarily give rise to structural changes that can be detected using MRI.


Another question might be why EAE, the go to mouse model neurologists love--does not create hypoperfusion.
HOWEVER, reducing blood flow in mice and creating hypoperfusion--damages white matter.

Furthermore, studies in rats have shown that reductions in blood flow to the cerebral hemispheres by 50% results in white matter damage with axon sparing [23]. Oligodendroglia are known to be especially susceptible to ischemic insults [24, 25]. A recent study in mice has demonstrated that even mild chronic hypoperfusion (blood flow reduction of 15%–25%) results in disruption of axon-myelin integrity with maldistribution of MAG as well as upregulation of pro-inflammatory genes [26].


Other MS specialists/pharma have looked at these hypointense lesions/ black holes in SPMS and found that interferons mitigate these hypointense lesions. http://brain.oxfordjournals.org/content ... 6.full.pdf
Which, as you point out, seems odd...since black holes are considered signs of axonal loss, and how could an interferon bring back axons?

Unless hypointense lesions are not just "black holes", but areas where cerebrospinal fluid is pooling, and pushing aside brain tissue. CSF shows up as dark in T1 MRI. I dunno...
cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
User avatar
cheerleader
Family Elder
 
Posts: 5092
Joined: Mon Sep 10, 2007 2:00 pm
Location: southern California

Re: A must read article (hypoperfusion stress)...

Postby 1eye » Fri Aug 02, 2013 2:42 pm

When the chicken gets eaten, the egg is not worried. It might be more important to ask, which came last...
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'MS' is over - if you want it
Patients sans/without patience
User avatar
1eye
Family Elder
 
Posts: 2997
Joined: Wed Mar 17, 2010 3:00 pm
Location: Kanata, Ontario, Canada

Re: A must read article (hypoperfusion stress)...

Postby 1eye » Fri Aug 02, 2013 8:49 pm

the MS brain needs less perfusion. MS causes hypoperfusion, 'cause less tissue needs less blood flow. It's the age old chicken and egg.

I think it's the age-old "who's smoking better drugs?"

interferons mitigate these hypointense lesions. http://brain.oxfordjournals.org/content/124/7/1396.full.pdf
Which, as you point out, seems odd...since black holes are considered signs of axonal loss, and how could an interferon bring back axons?

Didn't I read in one of those papers that black holes are *not* a sign of axonal loss, after all? What's the evidence either way? If interferons actually reduced them that would mean they are not permanent. If they reduced hypointense lesions, and they in turn were signs of disability due to axonal loss, why would Canadian neurologists refuse to prescribe them to people with disability progression, saying the interferons are no good for "SPMS"?
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'MS' is over - if you want it
Patients sans/without patience
User avatar
1eye
Family Elder
 
Posts: 2997
Joined: Wed Mar 17, 2010 3:00 pm
Location: Kanata, Ontario, Canada

Re: A must read article (hypoperfusion stress)...

Postby Cece » Wed Nov 06, 2013 3:18 pm

http://www.ncbi.nlm.nih.gov/pubmed/23243502
Cardiovasc Psychiatry Neurol. 2012;2012:367516. doi: 10.1155/2012/367516. Epub 2012 Dec 3.

Cardiovascular risk factors promote brain hypoperfusion leading to cognitive decline and dementia.

de la Torre JC.

Department of Psychology, University of TX at Austin, Austin, TX 78712, USA.

Abstract

Heart disease is the major leading cause of death and disability in the world. Mainly affecting the elderly population, heart disease and its main outcome, cardiovascular disease, have become an important risk factor in the development of cognitive decline and Alzheimer's disease (AD). This paper examines the evidence linking chronic brain hypoperfusion induced by a variety of cardiovascular deficits in the development of cognitive impairment preceding AD. The evidence indicates a strong association between AD and cardiovascular risk factors, including ApoE(4), atrial fibrillation, thrombotic events, hypertension, hypotension, heart failure, high serum markers of inflammation, coronary artery disease, low cardiac index, and valvular pathology. In elderly people whose cerebral perfusion is already diminished by their advanced age, additional reduction of cerebral blood flow stemming from abnormalities in the heart-brain vascular loop ostensibly increases the probability of developing AD. Evidence also suggests that a neuronal energy crisis brought on by relentless brain hypoperfusion may be responsible for protein synthesis abnormalities that later result in the classic neurodegenerative lesions involving the formation of amyloid-beta plaques and neurofibrillary tangles. Insight into how cardiovascular risk factors can induce progressive cognitive impairment offers an enhanced understanding of the multifactorial pathophysiology characterizing AD and ways at preventing or managing the cardiovascular precursors of this dementia.

Hypoperfusion is bad...
Cece
Family Elder
 
Posts: 9054
Joined: Mon Jan 04, 2010 3:00 pm

Re: A must read article (hypoperfusion stress)...

Postby cheerleader » Wed Nov 06, 2013 3:42 pm

Cece wrote:Hypoperfusion is bad...

yup. way bad. I used de la Torre's paper in this write up of CCSVI and diseases of neurodegeneration, using hypoperfusion as a constant variable in all --Parkinson's, Alzheimer's, vascular dementia and MS. I put de la Torre in touch with the ISNVD, hope he'll be a speaker sometime in the future. Dr. Paula Grammas will this February. Her publications on Alzheimer's and hypoperfusion make a strong case, too.

http://ccsvi.org/index.php/the-basics/c ... l-diseases

cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
User avatar
cheerleader
Family Elder
 
Posts: 5092
Joined: Mon Sep 10, 2007 2:00 pm
Location: southern California

Re: A must read article (hypoperfusion stress)...

Postby 1eye » Thu Nov 07, 2013 10:32 am

I have often thought: Find the cause and you are halfway to a solution. So if hypoperfusion is a common and central part of the puzzle: what causes that? Let's call it X. X causes the common
on thread of hypoperfusion in how many of these diseases? Is x maybe what makes them different?
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'MS' is over - if you want it
Patients sans/without patience
User avatar
1eye
Family Elder
 
Posts: 2997
Joined: Wed Mar 17, 2010 3:00 pm
Location: Kanata, Ontario, Canada


Return to Chronic Cerebrospinal Venous Insufficiency (CCSVI)

 


  • Related topics
    Replies
    Views
    Last post

Who is online

Users browsing this forum: Robnl, sbr487


Contact us | Terms of Service