New research: Flow means Go

We are just beginning to understand the brain's lymphatic vessels, and how this newly discovered system may be implicated in neurodegenerative diseases like MS.  It will be important to consider the mechanistic system which enables lymphatic drainage to mature and function.  In recent experiments conducted with mice, veins are implicated in lymphatic flow.  In fact, when mice had veins that did not drain, but had a reflux of blood flow---like what we see in CCSVI---lymph stopped flowing.  And lymph vessels stopped forming correctly, due to endothelial dysfunction.

From a press release from the Perelmen School of Medicine at the University of Pennsylvania's Kahn Lab-- on research published in The Journal of Clinical Investigation's August issue:
http://www.uphs.upenn.edu/news/News_Releases/2015/07/kahn/

Flow means "go" for proper lymph system development
PHILADELPHIA--The lymphatic system provides a slow flow of fluid from our organs and tissues into the bloodstream. It returns fluid and proteins that leak from blood vessels, provides passage for immune and inflammatory cells from the tissues to the blood, and hosts key niches for immune cells. How this system develops hasn't been well understood, but now researchers from the Perelman School of Medicine at the University of Pennsylvania have found from experiments in mice that the early flow of lymph fluid is a critical factor in the development of mature lymphatic vessels.  

The project was prompted in part by recent studies of cultured lymphatic vessel endothelial cells that suggested that fluid forces could be an important factor in the maturation of lymphatic vessels. But there was no straightforward way to test this hypothesis in live animals. 

"No one had been able to come up with a way to stop lymph flow in embryonic animals, without preventing their lymphatic vessels from developing in the first place," said first author Daniel T. Sweet, PhD, a postdoctoral fellow in the Kahn Laboratory.

In humans and other mammals, the lymphatic system is a low-flow system that, unlike the blood circulatory system, has no central pump. Instead it relies on muscular contraction of the mature lymphatic vessel wall and small valves in lymphatic vessels to squeeze fluid along and prevent backflow.

Larger collecting lymphatic vessels receive many small inflows from lymphatic capillaries in surrounding tissues. "You can't just close one of the vessels to block flow downstream--there are many other tributaries coming in," said Sweet.

The solution to testing the role of flow in developing lymphatic vessels turned out to be a line of transgenic mice, developed earlier by the Kahn laboratory. Lacking a gene called Clec2, the mice fail to produce a certain receptor on blood platelets, with a remarkable result: veins that normally help drain the lymph system leak back into it. Like an ocean tide surging into a river, this upstream flow of blood stops the usual downstream flow of lymph.

What's more, the researchers found that smooth muscle cells, which normally form a thin lining in mature lymphatic vessels, and perform contractions that help lymph flow, instead formed an abnormally thick lining, as if the usual signal to shut off cell proliferation were missing. 

"We started off thinking that flow might have a role just in valve formation, but ended up realizing that flow is really controlling all aspects of the maturation of these lymphatic vessels," said Sweet.

If flow is essential for a healthy lymphatic cleansing system---which we now know is part of the brain as well as other organs---the lack of venous drainage for the brain and spine could have disaterous affects on immune cells and metabolite cleansing processes. And reflux and slowed flow of venous blood in the jugular veins--as noted in CCSVI--could be shutting down the lymphatic drainage system of the brain.  Endothelial dysfunction, which has also been noted in MS, also plays a role in the cessation of lymphatic flow.  Flowing fluids create shear stress, and are needed for healthy endothelial cells.  It's a virtuous cycle.

Venous flow matters. Jugular flow matters. Lymphatic vessel flow matters.  The basic science is being established.


Joan

New research: MS as a disease of Endothelial Dysfunction

We have a brand new peer-reviewed paper from the researchers of the ISNVD which is considering the vascular connection to MS.  It is called:
"Blood circulating microparticle species in relapsing–remitting and secondary progressive multiple sclerosis. A case–control, cross sectional study with conventional MRI and advanced iron content imaging outcomes" This paper is published in the Journal of Neurological Sciences.
http://www.jns-journal.com/article/S0022-510X%2815%2900309-3/abstract

The researchers looked at serum markers of healthy individuals and compared them to people with MS. (Can I just inject a "Hallelujah" here?  This was my dream eight years ago, and it is now a reality.)  What they found were that in people with MS, there are circulating microparticles in the blood that aren't found in healthy people.  These markers  (CD31+/CD51+/CD61+/CD54+)  are microparticles which are shed from the lining of the damaged endothelium.  We see the same markers in cardiovascular disease.  These markers are associated with coronary artery disease, hypercoagulation, thrombosis (clotting) and stroke.
http://onlinelibrary.wiley.com/doi/10.1111/j.1538-7836.2010.04007.x/full

Endothelial microparticles (EMP) are shed by dying and injured endothelial cells.  They cause hypercoagulation, inflammation and contribute to vascular disease.   They slow blood flow.
http://atvb.ahajournals.org/content/31/1/27.abstract

It's been eight years since I first put together research on MS as a disease connected to blood flow and the vascular system.  What I saw in Jeff's blood results when he was diagnosed during his first severe flare---hypercoagulation, high c reactive protein, high inflammatory markers---looked to me like a vascular reaction caused by endothelial dysfunction.  I sent the research I compiled to university researchers, and created a nutrition and lifestyle program for Jeff, to address this issue.  My hope was that he could find stability in his disease process, by reducing the impact of vascular endothelial dysfunction.  I saw that cardiovascular researchers, like Dr. John Cooke, were having great success with their heart patients, and that encouraged me!  And sure enough, after three months on the Endothelial Health Program, Jeff's serum markers of endothelial dysfunction were lowered, and his MS stayed in remission.

What I saw in Jeff's serum markers was real.  Although his neurologist claimed it had "nothing to do with MS"---it appears that wasn't true, and Jeff is not alone.  These markers were shown to be correlated with lesions and brain atrophy in MS using SWI and MRI scans.

Here is the conclusion from the researchers:  These results indicate that circulating microparticles' profiles in MS may support mechanistic roles for microvascular stress and injury which is an underlying contributor not only to MS initiation and progression, but also to pro-inflammatory responses.

This means that stress and injury to the endothelial lining, also known as endothelial dysfunction, may be a contributor to MS initiation and progression.

The good news is that there are things we can all do today to reduce endothelial dysfunction,  cellular stress and injury and bring these serum markers down.  The hope is that by helping the endothelium heal, we can limit microparticle shedding into the blood, and reverse this inflammatory process.

What would be the next step?  Retest the microparticle levels in pwMS after they have been on the endothelial health program for months/years---and see if this correlates to a slowing or stopping of MS disease progression.  If Jeff is any indication, there is great hope. 

Here's the Endothelial Health Program.
http://ccsvi.org/index.php/helping-myself/endothelial-health

Talk to your own doctor, see if it might be something you can do.  I am not a doctor, so it's always best to consult one before beginning a new regimen!  Keep an eye on your blood levels of Crp, hypercoagulation, d-dimer, AST and ALT, and serum cholesterol--as well as vitamin D and B12 levels.  

Keep learning, keep moving and keep hoping!  More answers ahead,

Joan