CNS capillaries

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

CNS capillaries

Postby Cece » Mon Sep 12, 2011 12:00 pm

Let's pool what we know about CNS capillaries. (CNS meaning central nervous system meaning brain and spine, although I am specifically thinking about the brain.)

http://books.google.com/books?id=ElwTtS ... &q&f=false

The endothelial cells are bonded by tight junctions that bar the passage of high molecular weight substances. This is what is generally meant by the blood brain barrier. Unlike capillaries of the general circulation, choroid plexus cells have no intercelluar pores and no fenestrations.
The brain capillary bed is enormous, and has been estimated to cover the area of a tennis court.


Considering the earliest legion of MS is microvascular and considering the ease with which microvessels may be isolated from MS human autopsy brain plaque tissue (Pardridge et al, 1987; Washington et al, 1994), it is somewhat surprising that there are so few studies on the immunology and biochemistry of capillaries isolated from MS plaque tissue.

http://www.jneurovirol.com/pdf/5%286%29/556-569.pdf

Somewhat surprising! As if an entire area of possible research, from which possible treatment could arise, had been neglected.

Ok, some interesting things found, but still no clarity on whether or not brain capillaries lack smooth muscle cells. 1eye, I am trying.

Once inside the capillary endothelial cell, the virus may enhance the progression of disease by causing BBB disruption which then facilitates the entry into brain of circulating plasma proteins, which are toxic to astrocytes (Nadal et al, 1995), and circulating immune cells (Soilu-Hanninen et al, 1994).

Similar to a virus disruption, CCSVI disrupts the flow which disrupts the microvasculature in this way. 'Circulating plasma proteins' leak across the BBB and are toxic to astrocytes. Circulating immune cells get across in the same way. But once CCSVI is treated and healthy blood flow is restored, this may heal, and we may in time be well.

Pre-capillary arteriolar smooth muscle cells and capillary pericytes express DR-antigen, indicating antigen presentation in the brain occurs distal to the capillary endothelium.

In the not-as-small-as-a-capillary arterioles, there are smooth muscle cells; but in the capillaries, is it that there are no smooth muscle cells but there are pericytes instead? What is a pericyte?
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Re: CNS capillaries

Postby Cece » Mon Sep 12, 2011 12:05 pm

Capillary pericytes in brain are said to have a
contractile function and to be the smooth muscle
analog of the capillary. Contractile cells such as
smooth muscle cells express the a-actin isoform.
The a-actin gene is expressed in brain capillary
pericytes grown in tissue culture (Herman and
D'Amore, 1985). However, immunoreactive a-actin
is not expressed in pericytes in vivo in microvessels
of bovine retina (Nehls and Drenckhahn, 1991).

It was in the same article. Pericytes are what the capillary in the brain has instead of smooth muscle cells. We are not at risk of intimal hyperplasia of the capillaries. One less thing to worry about. :)

1eye, your thoughts about smooth muscle cells in capillaries was always having to do with contraction and dilation, right, and how the capillaries might affect flow?
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Re: CNS capillaries

Postby SaintLouis » Mon Sep 12, 2011 7:31 pm

Sorry if this is a a dumb-dumb question, I've not followed this train of thought but it occured to me, do anti-histamines constrict the cappilaries in the CNS bed? Might that help "tighten" the endothelium?
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Re: CNS capillaries

Postby David1949 » Mon Sep 12, 2011 7:51 pm

Elsewhere in the body, antibodies can pass between the endothelium cells which line the capillaries. But in the brain the cells of the endothelium are more tightly connected so that antibodies cannot pass through. They call that the blood brain barrier, BBB. But in those of us with MS, antibodies do get past the BBB and once there they begin attacking the myelin covering of the nerve cells. (Lucky us) :-(

So if the autoimmune theory is correct then the problem has to start with the breaching of the BBB. If the antibodies can't get past the BBB then they can't hurt us.
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Re: CNS capillaries

Postby 1eye » Mon Sep 12, 2011 7:56 pm

These pericytes: are they in this huge capillary bed in the brain only? Or are they in other organs as well? Is there any difference between capillaries on the venous side and those on the arterial side? The flow is in a different direction. I was thinking about flow control. In linear electronics it is done by diodes (really valves - the di prefix had to do with their construction when they were made out of tubes) and transistors (or triodes). But there isn't much that's equivalent to a smooth muscle changing blood vessel diameter. Not much in electronics has a 4th-power relationship, although much is possible now with digital signal processing. It must consume a lot of power to do that, and if it is disrupted, pericytes or smooth muscles, that part of the body would lose control of a large amount of power. That's where the brain comes in as far as fatigue goes, I believe. If the devices that control flow to the parts of the brain that control flow elsewhere in the body (autonomic nerves that dilate peripheral blood vessels), zap, you lose power.

Are pericytes what is vulnerable to or damaged by reflux? Is the lack of actin the reason why cows are slow? Is that a genetic target of CCSVI/"MS"?
"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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More about endothelial disfunction

Postby frodo » Thu Sep 15, 2011 12:52 pm

I find the endothelial disfunction in MS a very interesting subject. Even if CCSVI theory is finally proven wrong, there must be something about those vascular capillaries. I find really interesting the question about how the antibodies enter the CNS. The study of the endothelial could be the link between the pure-autoimmune theory and CCSVI.

I have found a couple of articles that relate endothelial problems with the Normal Appearing White Matter (NAWM). Both come from the same group

http://www.ncbi.nlm.nih.gov/pubmed/17239011
http://www.ncbi.nlm.nih.gov/pubmed/11958369
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Re: CNS capillaries

Postby Cece » Fri Sep 16, 2011 4:24 pm

Neuropathol Appl Neurobiol. 2007 Feb;33(1):86-98.

Persistent endothelial abnormalities and blood-brain barrier leak in primary and secondary progressive multiple sclerosis.

Leech S, Kirk J, Plumb J, McQuaid S.

SourceMultiple Sclerosis and Inflammation Research Groups, School of Medicine and Dentistry, Queens University Belfast, Institute of Pathology, Belfast, UK.

Abstract

Epithelial and endothelial tight junctions are pathologically altered in infectious, inflammatory, neoplastic and other diseases. Previously, we described such abnormalities, associated with serum protein leak, in tight junctions of the blood-brain barrier endothelium, in lesional and normal-appearing white matter (NAWM) in secondary progressive (SP) and acute multiple sclerosis (MS). This work is extended here to lesions and NAWM in primary progressive multiple sclerosis (PPMS) and to cortical grey matter in PPMS and SPMS.

Immunocytochemistry and semiquantitative confocal microscopy for the tight junction protein zonula occludens 1 (ZO-1) was performed on snap-frozen sections from PPMS (n = 6) and controls (n = 5). Data on 2103 blood vessels were acquired from active lesions (n = 10), inactive lesions (n = 15), NAWM (n = 42) and controls (n = 20). Data on 1218 vessels were acquired from normal-appearing grey matter (PPMS, 5; SPMS, 6; controls, 5). In PPMS abnormal ZO-1 expression in active white matter lesions and NAWM, was found in 42% and 13% of blood vessels, respectively, comparable to previous data from acute and SPMS. In chronic white matter plaques, however, abnormalities were considerably more frequent (37%) in PPMS than in SPMS. Abnormality was also more frequent in normal-appearing grey matter in SPMS (23%) than in PPMS (10%). In summary, abnormal tight junctions in both SPMS and PPMS are most frequent in active white matter lesions but persist in inactive lesions, particularly in PPMS. Abnormal tight junctions are also common in normal-appearing grey matter in SPMS. Persistent endothelial abnormality with leak (PEAL) is therefore widespread but variably expressed in MS and may contribute to disease progression.


It's interesting to consider if there are differences in the endothelium between SPMS and PPMS or between RRMS and PPMS. Maybe CCSVI creates a certain environment but our bodies or our endotheliums respond to that environment differently

What do you think of that name, too! PEAL or persistent endothelial abnormality with leak.
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Re: CNS capillaries

Postby Cece » Fri Sep 16, 2011 4:29 pm

Brain Pathol. 2002 Apr;12(2):154-69.

Abnormal endothelial tight junctions in active lesions and normal-appearing white matter in multiple sclerosis.

Plumb J, McQuaid S, Mirakhur M, Kirk J.

SourceNeuropathology Laboratory, Royal Group of Hospitals Trust, Belfast, Northern Ireland, United Kingdom.

Abstract

Blood-brain barrier (BBB) breakdown, demonstrable in vivo by enhanced MRI is characteristic of new and expanding inflammatory lesions in relapsing-remitting and chronic progressive multiple sclerosis (MS). Subtle leakage may also occur in primary progressive MS. However, the anatomical route(s) of BBB leakage have not been demonstrated. We investigated the possible involvement of interendothelial tight junctions (TJ) by examining the expression of TJ proteins (occludin and ZO-1 ) in blood vessels in active MS lesions from 8 cases of MS and in normal-appearing white (NAWM) matter from 6 cases. Blood vessels (10-50 per frozen section) were scanned using confocal laser scanning microscopy to acquire datasets for analysis. TJ abnormalities manifested as beading, interruption, absence or diffuse cytoplasmic localization of fluorescence, or separation of junctions (putative opening) were frequent (affecting 40% of vessels) in oil-red-O-positive active plaques but less frequent in NAWM (15%), and in normal (< 2%) and neurological controls (6%). Putatively "open" junctions were seen in vessels in active lesions and in microscopically inflamed vessels in NAWM. Dual fluorescence revealed abnormal TJs in vessels with pre-mortem serum protein leakage. Abnormal or open TJs, associated with inflammation may contribute to BBB leakage in enhancing MRI lesions and may also be involved in subtle leakage in non-enhancing focal and diffuse lesions in NAWM. BBB disruption due to tight junctional pathology should be regarded as a significant form of tissue injury in MS, alongside demyelination and axonopathy.

Tight junction abnormalities in 40% of vessels in active plaques, 15% of vessels in normal appearing white matter, and less than 2% of vessels in those ever-lucky "normals."

This is very supportive of research into CCSVI, since there is logic to explain how CCSVI can cause tight junction abnormalities in the endothelium of the capillaries of the brain.
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Re: CNS capillaries

Postby frodo » Sat Sep 17, 2011 2:28 am

Cece wrote:It's interesting to consider if there are differences in the endothelium between SPMS and PPMS or between RRMS and PPMS. Maybe CCSVI creates a certain environment but our bodies or our endotheliums respond to that environment differently

What do you think of that name, too! PEAL or persistent endothelial abnormality with leak.


For sure it is apPEALing!!!
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Re: CNS capillaries

Postby Cece » Sat Sep 17, 2011 9:28 am

Diapedesis is another word for the leakage across the capillaries. Diapedesis is not in itself an abnormality, but the abnormal blood flow creates an abnormal degree of diapedesis, which is the persistent endothelial abnormality with leak. The question is whether the unappealing :) condition of PEAL corrects itself, once the CCSVI blockages have been corrected.

Two useful research articles. I will have to remember them.
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