Welcome! This blog contains research & information on lifestyle, nutrition and health for those with MS, as well as continuing information on the understanding of the endothelium and heart-brain connection. This blog is informative only--all medical decisions should be discussed with your own physicians.

The posts are searchable---simply type in your topic of interest in the search box at the top left.

Almost all of MS research is initiated and funded by pharmaceutical companies. This maintains the EAE mouse model and the auto-immune paradigm of MS, and continues the 20 billion dollar a year MS treatment industry. But as we learn more about slowed blood flow, gray matter atrophy, and environmental links to MS progression and disability--all things the current drugs do not address--we're discovering more about how to help those with MS.

To learn how this journey began, read my first post from August, 2009. Be well! Joan

Showing posts with label endothelial cells. Show all posts
Showing posts with label endothelial cells. Show all posts

Tuesday, September 22, 2015

Melatonin and MS

New research shows the connection between low levels of melatonin, known as the sleep hormone, and MS relapses.

Melatonin is the hormone which helps encourage our sleep state.   It is made by the pineal gland in our brains, and it needs the visual cue of darkness in order to begin production.  We naturally produce more melatonin in the fall and winter months, because darkness is more prevelant.  This is why we might find ourselves sleepier and more likely to want to hibernate during these darker months, because our brain is cranking out melatonin.

New research is linking this lower level of melatonin found in spring and summer to seasonal relapses in MS.
http://www.cell.com/cell/fulltext/S0092-8674(15)01038-7

It appears that in humans with MS, the lower levels of melatonin found in their blood during the sunnier months might be linked to MS progression and relapse rate.  That is, there is a correlation between seasonal low melatonin levels and clinical relapses.  (It's always important to make the distinction between correlation and causation---  the researchers are just noticing that in people with lower levels of melatonin, there were more frequent relapses...but, if you read this whole post, I hope I'll explain why this might be.)  Don't go out and buy melatonin just yet!

The researchers who are studying melatonin weren't quite sure why it is so helpful to people with MS.   So, they go to the EAE model of MS in mice and studying t-cell modulation.  ARGHHH!!!!   Why???

We don't need to look at EAE in mice---we already have a correlation of melatonin levels in brain health for HUMANS.

When we look at MS as a disease like stroke in humans, where hypoxic injury and reperfusion injury damage the endothelial layer of the brain's blood vessels....it all makes sense.

Because melatonin protects the brain's endothelial cells under hypoxic and oxidative stress conditions.
http://www.hindawi.com/journals/omcl/2014/639531/


Melatonin has a cellular protective effect in cerebrovascular and neurodegenerative diseases. Protection of brain endothelial cells against hypoxia and oxidative stress is important for treatment of central nervous system (CNS) diseases, since brain endothelial cells constitute the blood brain barrier (BBB). In the present study, we investigated the protective effect of melatonin against oxygen-glucose deprivation, followed by reperfusion- (OGD/R-) induced injury, in bEnd.3 cells. The effect of melatonin was examined by western blot analysis, cell viability assays, measurement of intracellular reactive oxygen species (ROS), and immunocytochemistry (ICC). Our results showed that treatment with melatonin prevents cell death and degradation of tight junction protein in the setting of OGD/R-induced injury. In response to OGD/R injury of bEnd.3 cells, melatonin activates Akt, which promotes cell survival, and attenuates phosphorylation of JNK, which triggers apoptosis. Thus, melatonin protects bEnd.3 cells against OGD/R-induced injury.


Now in plain English---melatonin protects the endothelial cells of the blood brain barrier, and keeps those endothelial cells alive during times of of low oxygen and low glucose delivery--- so they can protect the brain.  Melatonin is a known anti-oxidant.  Just like fruits and vegetables.  

Another connection could be that people with MS who have lower levels of melatonin just aren't getting enough good sleep---and that could be the connection to higher relapse rates.  Especially now that we understand how the brain's lymphatic cleansing system works only when we sleep.

To complicate and confuse matters---melatonin has an inverse relationship with vitamin D.  In research in people with MS, it was shown that people taking higher Vitamin D supplementation had lower levels of melatonin. 

But we also know that lower vitamin D rates are correlated with MS relapses.  So, what's a human with MS to do?  Take melatonin???  Bump up vitamin D?  Do both?  How much?  When?  How...?  Light?  Dark?  

Bottom line:  Both melatonin and vitamin D are hormones which are also anti-oxidants, decrease inflammation and address oxidative stress. 

Long-time readers of this blog will know that it's never about one pill or supplement, it's about living a complete lifestyle which encourages endothelial health.   It's all about balance. And there are many ways to accomplish this.  

It's difficult to double-blind and research a complete lifestyle----which is why researchers will pick one aspect at a time---like Vitamin D levels, or melatonin levels, or cholesterol levels.  You get the picture.  

Have your vitamin D levels tested.  If they are low, supplement and get some UV ray therapy.  If you have trouble sleeping, or are jet-lagged,  talk to your doctor about possibly adding melatonin to your regimen.  But remember to move, and eat whole and colorful foods, and laugh, and reduce stress, and get good sleep.  It's a complete lifestyle, and no one pill or supplement can replace that.

Be well!
Joan





Wednesday, February 25, 2015

Putting the Pieces Together

In my last blog post, I asked WHY cerebral circulation time might be doubled in people with MS.  In this post, I'm going to attempt to answer this question, using recent peer-reviewed research.  Because the answers are out there, we just need to put the pieces together.

A recent study published in JAMA Neurology Journal by Yulin Ge, MD showed how pwMS had impaired cerebrovascular function.  Dr. Ge is a member of the International Society for Neurovascular Disease.  Dr. Ge has been imaging the MS brain for over a decade at NYU, and has found many vascular connections.

Impaired Cerebrovascular Reactivity in Multiple Sclerosis
http://archneur.jamanetwork.com/article.aspx?articleid=1893478

Now, to explain what Dr. Ge and his fellow researchers at NYU found.  CVR is how the brain reacts or responds with blood flow when there is vasodilation in blood vessels.  This function is extremely important, as neurons need adequate blood flow to provide glucose and oxygenation.  Without this response of adequate cerebral bloodflow (CBF), the brain will not function properly, and neurons can potentially die.

Patients with MS had a significant decrease of cerebrovascular reactivity compared with controls. This decrease in CRV correlated to gray matter atrophy, but did not correlate with white matter lesions. 

Their conclusion was that there is an impairment in the cerebrovascular pathophysiology in pwMS, and that inadequate blood flow to neurons may indeed be the cause of neurodegeneration in MS.  And that this was a vascular problem, NOT a problem initiated by white matter lesions.  Something was wrong with the blood vessels response.  Increased blood flow did not happen when it was needed.


Impaired CVR would most certainly cause a delay in cerebral circulation time!  These two conditions are intertwined.

Another study on impaired CVR looked at why this might be happening.
A Columbia University study, published last summer, found that when researchers damaged the vascular endothelial cells lining the blood vessels using lasers to cause oxidative stress,  they could disrupt blood flow to the brain and affect neurovascular coupling.  http://ccsviinms.blogspot.com/2014/06/columbia-researchers-provide-new.html

Did you catch that??
Damaged endothelial cells in blood vessels changes neurovascular coupling, and cerebral blood flow is reduced.

“Our latest finding gives us a new way of thinking about brain disease—that some conditions assumed to be caused by faulty neurons could actually be problems with faulty blood vessels,” Hillman adds. “This gives us a new target to focus on to explore treatments for a wide range of disorders that have, until now, been thought of as impossible to treat. 

Endothelial cell death and dysfunction may well be the cause of slowed cerebral blood circulation time in MS.  That's all it took in the Columbia study--frying the endothelial cell layer with lasers and slowed down cerebrovascular reactivity, because the endothelial layer could no longer respond with vascodilation and more blood flow to the brain. This is endothelial dysfunction.

Dr. Zamboni has noted that there is a derangement of the endothelial cell layer in the jugular veins and valves in people with CCSVI/MS.  This loss of endothelial cells could well be causing the decrease in cerebrovascular reactivity seen in people with MS.  And it is caused by CCSVI.
http://phl.sagepub.com/content/early/2014/06/27/0268355514541980.abstract


Here are my proposed steps as to why pwMS have delayed cerebral circulation time.

1. Loss of laminar flow, refluxive blood flow and oxidative stress causes endothelial cell death and dysfunction in the vessel walls of both arteries and veins.
2. Without endothelial cells in blood vessels, cerebrovascular reactivity is decreased.
3. This decrease in CVR leads to a slowed cerebral circulation time.
4. Slowed blood flow leads to neuronal cell death and brain atrophy, as well as an hypoxic situation which creates white matter lesions and inflammation.  Voila.  MS.


The research is out there.  If someone could please send this to "The Mouse Doctor" at Barts--he is not taking any responses from me on his blog.  But at least he is FINALLY looking at blood flow.
http://multiple-sclerosis-research.blogspot.com/2015/02/is-ms-starving-brain.html

Of course CCSVI could be implicated in CVR and slowed cerebral circulation time in MS.
How to learn more?  Test patients, like my husband, who have had venous malformations repaired and see if their cerebral circulation time is closer to normal.  My husband's reversal of gray matter atrophy as shown on MRI would seem to imply that there has been healing.

If you want some GREAT news---Dr. John Cooke's team is now figuring out how to create healthy new endothelial cells from fibroblasts, which could then be implanted in patients.
http://www.genengnews.com/gen-news-highlights/fibroblast-transformed-endothelial-cells-show-promise-for-damaged-tissue-repair/81250576/

But what do I know?
It's only been seven years since I contacted Dr. Cooke at Stanford and asked him what he thought about endothelial dysfunction in MS.
http://ccsvi.org/index.php/helping-myself/endothelial-health
Joan