getting to know your blood-brain barrier

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

getting to know your blood-brain barrier

Postby Cece » Sat Aug 20, 2011 10:41 pm

http://en.wikipedia.org/wiki/Blood-brain_barrier
The blood–brain barrier (BBB) is a separation of circulating blood and the brain extracellular fluid (BECF) in the central nervous system (CNS). It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion of microscopic objects (e.g. bacteria) and large or hydrophilic molecules into the cerebrospinal fluid (CSF), while allowing the diffusion of small hydrophobic molecules (O2, hormones, CO2). Cells of the barrier actively transport metabolic products such as glucose across the barrier with specific proteins. This barrier also includes a thick basement membrane and astrocytic endfeet.

Thick basement membrane? Astrocytic endfeet? Brain extracellular fluid? And that's only the first paragraph....
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Postby NZer1 » Sun Aug 21, 2011 2:54 pm

This is also about the BBB leakage and covers the CCSVI linkage as well in David Hubbards Video.

Zonulin?

https://www.facebook.com/topic.php?topi ... 4#post1367
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Postby jimmylegs » Sun Aug 21, 2011 4:52 pm

Cellular Tight Junctions as Mediators of Adverse Effects
http://onlinelibrary.wiley.com/doi/10.1 ... 9/abstract

Tight junctions are highly complicated and finely regulated structures that provide for the barrier and exchange functions of epithelia and endothelia at the interface between the internal organs and the external environment, and are therefore frequently exposed to noxious stimuli. Recent evidence points to epithelial and endothelial barrier dysfunction, resulting from changes in structure of the tight junctions, as an important early toxic event, preceding more severe damage to the cells. Increased tight junction permeability has also been implicated in the pathogenesis of several multifactorial diseases, frequently involving an exaggerated inflammatory response. Some examples of tight junction alterations occurring after exposure to toxic stimuli, including ethanol, heavy metals and oxidative stress, will be discussed in more detail. In addition, the implications of barrier dysfunction in pathological conditions including hereditary disorders of tight junction proteins, cancers, microbial infections, inflammatory bowel disease, multiple sclerosis and coeliac disease will be presented.

"zinc deficiency was found to interfere with tight and adherens junction formation by delocalization of ZO-1"
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Postby Cece » Sun Aug 21, 2011 5:04 pm

You guys are awesome.
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Postby fee001 » Sun Aug 21, 2011 6:03 pm

Hi!

I am not clued up on BBB but whether this is relevant I dont Know.
Before my Atlas was adjusted my gums had bled badly for 9 or 10 years, as soon as Atlas adjusted, stopped overnight never to return.

and the bloodflow to my body increased.

Gosh you all use like complex words and abbreviations to me, way over my head, so I havent read any previous writings about it all, way to complex for someone so simple eh! and I know a limited amount, how a novice would cope I do not know

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Postby NZer1 » Sun Aug 21, 2011 6:08 pm

I'd never heard of it, but it's action has been known for ages..Zonulin
From Wikipedia, the free encyclopedia

Zonulin is a protein that participates in tight junctions between cells of the wall of the digestive tract. Initially discovered in 2000 as the target of zonula occludens toxin, secreted by cholera pathogen Vibrio cholerae,[1] it has been implicated in the pathogenesis of coeliac disease[2] and diabetes mellitus type 1.[3] It is being studied as a target for vaccine adjuvants.[4] ALBA Therapeutics is developing a zonulin receptor antagonist, AT-1001, that is currently in phase 2 clinical trials.
[edit] References




^ Wang, W; Uzzau, S; Goldblum, SE; Fasano, A (2000). "Human zonulin, a potential modulator of intestinal tight junctions". Journal of cell science 113 Pt 24: 4435–40. PMID 11082037.



^ Thomas, KE; Sapone, A; Fasano, A; Vogel, SN (2006). "Gliadin stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent: role of the innate immune response in Celiac disease". Journal of immunology (Baltimore, Md. : 1950) 176 (4): 2512–21. PMID 16456012.



^ Sapone, A; De Magistris, L; Pietzak, M; Clemente, MG; Tripathi, A; Cucca, F; Lampis, R; Kryszak, D et al. (2006). "Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives". Diabetes 55 (5): 1443–9. doi:10.2337/db05-1593. PMID 16644703.



^ De Magistris, MT (2006). "Zonula occludens toxin as a new promising adjuvant for mucosal vaccines". Vaccine 24 Suppl 2: S2–60–1. PMID 16823929.

It appears that Zonulin is involved in the junction of the Endothelial cells in Veins as well, so there seems to be something here. The connection to the Brain barrier for some reason was over looked by researchers focused on one problem rather than a global look at the Endothelial cells around the body.
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Postby Cece » Sun Aug 21, 2011 6:34 pm

It appears that Zonulin is involved in the junction of the Endothelial cells in Veins as well, so there seems to be something here.

If I'm following this right, Zonulin is a drug that could be of use in tightening up the blood-brain barrier? And it has not been tested for what benefit it might have to MS patients, who have a defective BBB.
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Postby jimmylegs » Sun Aug 21, 2011 6:46 pm

it's been a couple years anyway since i posted this so here it is again :)

Image

ps tight junctions are zonula occludens, adherens junctions are zonula adherens

source (with lots more great info):
http://cellbiology.med.unsw.edu.au/unit ... re0808.htm
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Postby jimmylegs » Sun Aug 21, 2011 6:50 pm

zonulin is a human protein AFAIK.
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Postby cheerleader » Sun Aug 21, 2011 7:09 pm

increased zonulin=bad for BBB....


Dr. Hubbard discussed research into zonulin in his presentation at the conference. As many of you know, the Hubbard Foundation recommends a gluten-free diet to maintain endothelial integrity and a healthy blood brain barrier.

So, what is gluten?? Gluten is a special type of protein that is commonly found in rye, wheat, and barley. Therefore, it is found in most types of cereals and in many types of bread. Not all foods from the grain family, however, contain gluten. Examples of grains that do not have gluten include wild rice, corn, buckwheat, millet, amaranth, quinoa, teff, oats, soybeans, and sunflower seeds.

If you're like me, you've probably wondered, "What the heck does gluten have to do with the brain?"
Well, there is a very interesting connection, and it's based on research being done at the University of Maryland on a protein called zonulin.

Zonulin is increased in our blood when we eat foods that contain glutens--
link

EVEN IF YOU DO NOT HAVE CELIAC DISEASE OR A GLUTEN ALLERGY, ZONULIN WILL AFFECT YOU.

Zonulin works as a gatekeeper in the intestine and also in the blood brain barrier. The more zonulin you have in your blood, the more permeable the tight junctions of your blood vessels become. Not a good thing, if we want to maintain a healthy lining in our guts, and blood brain barrier.

So, the basic message is...try not to eat foods that contain glutens. If pwMS have a venous system that refluxes and creates inflammation, we need to do everything in our power to keep those blood vessels healthy, strong and non-permeable. And avoiding gluten and the zonulin it creates, is a terrific thing to do!


Researchers find increased zonulin levels among celiac disease patients
Researchers at the University of Maryland School of Medicine have found that the human protein zonulin, which regulates the permeability of the intestine, is at increased levels during the acute phase of celiac disease. The discovery suggests that increased levels of zonulin are a contributing factor to the development of celiac disease and other autoimmune disorders such as insulin dependent diabetes, multiple sclerosis, andrheumatoid arthritis. The findings are published in the April 29 issue of the journal Lancet.

"Zonulin works like the traffic conductor or the gatekeeper of our body's tissues," says lead author Alessio Fasano, M.D., professor of pediatrics and physiology at the University of Maryland School of Medicine, and director of Pediatric Gastroenterology and Nutrition at the University of Maryland Hospital for Children. "Our largest gateway is the intestine with its billions of cells.

Earlier research conducted by Dr. Fasano discovered that zonulin is also involved in the regulation of the impenetrable barrier between the blood stream and the brain, known as the blood-brain barrier. Celiac disease offered Dr. Fasano and his team a unique model for understanding the dynamic interaction between zonulin and the immune system. Celiac disease is a genetic disorder that affects one out of every 300 people in Europe, but its prevalence in the United States is not fully known. People who suffer from the disorder are unable to eat foods that contain the protein gluten, which is found in wheat and other grains. The gluten sets off a reaction that can cause diarrhea, abdominal pain, malabsorption of nutrients, and other gastrointestinal problems. Celiac disease can be easily treated by avoiding foods with gluten.

I wrote this up on FB
link
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Postby Cece » Sun Aug 21, 2011 7:44 pm

Gluten-free, sigh. I like gluten....

Here was a website that I ran across with a lot of tasty-sounding gluten-free recipes:
http://glutenfreegoddess.blogspot.com/
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Postby jimmylegs » Sun Aug 21, 2011 8:16 pm

you can make sure your diet and supp regimen is balanced appropriately to optimize zinc status :)
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Postby NZer1 » Sun Aug 21, 2011 9:08 pm

Thank you everyone.
In my mind there are two parts to this problem.

One is the weakened walls through for instance gluten effect on zonulin.

Two is the repeated breach which is likely to be a pressure related issue causing a weak spot to become problematic over time, therefore there would be low flow and blockage or re-fluxing and breaching.

With this happening the natural repair would be from blood supplied components. If there is a slow flow that is also re-fluxing then the healing or strengthening of the breach would be delayed.

After writing this I think that the Dr Schelling version of breach caused by 'violent' flow problems is more likely. If it was purely an issue of leakage in weak places why would the lesions also be occurring in main flow veins and in the central brain rather than the external areas where there is the lowest flow volumes.

I think that the area of the brain that is most often having lesion formation and on what 'size' or 'flow capacity' is going to answer this. I would also imagine that Dr. Schelling has already answered this as well. It is the repeating breach that is causing progression over time in the true forms of MS, SP and PP, so it is the slow disease that will answer this one.
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Postby NZer1 » Sun Aug 21, 2011 9:32 pm

From http://www.umm.edu/news/releases/zonulin.htm

Earlier research conducted by Dr. Fasano discovered that zonulin is also involved in the regulation of the impenetrable barrier between the blood stream and the brain, known as the blood-brain barrier.

With celiac disease, the body reacts to gluten by creating antibodies that attack the intestine and cause severe damage over time. Unlike other autoimmune disorders, scientists also know that celiac disease is triggered by a specific antigen, which is the protein gluten. Celiac disease is also known to cause increased permeability of the intestine. In addition, many people who suffer from celiac disease also suffer from other autoimmune disorders.

"With celiac disease, we could never understand how a big protein like gluten was getting through to the immune system. Now we have the answer," explains Dr. Fasano. "People with celiac have an increased level of zonulin, which opens the junctions between the cells. In essence, the gateways are stuck open, allowing gluten and other allergens to pass. Once these allergens get into the immune system, they are attacked by the antibodies," adds Dr. Fasano.

"I believe that zonulin plays a critical role in the modulation of our immune system. For some reason, the zonulin levels go out of whack, and that leads to autoimmune disease," explains Fasano.

"We are at the threshold of exciting discoveries in this field," says Dr. Fasano. "We now have a new way of looking at our cells. Our cells are not stacked together like bricks. They are a dynamic field, which is constantly in flux."
==============================================
After reading the above I get the impression that the 'gateway' effect stays open?
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Postby CD » Sun Aug 21, 2011 9:34 pm

The costly new drug will probably turn out to be plain old Zinc. It is an antagonist inhibitor and can chelate heavy metals that are toxic.
Where there is a will, there is a way. "HOPE"

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