CNS lymph vessels found. Brain is not immune-privileged

[cheerleader]

Here's a great write up of the discovery from the NIH--sponsers of Dr. Nedergaard's (g)lymphatic research, as well as the Kipnis Lab study which discovered the lymph vessels--on how these two recent discoveries are linked, and how this will change neurological disease studies.

http://www.nih.gov/researchmatters/june ... phatic.htm


cheer

[1eye]

Questions I need answers to:

1. if lymphatic waste clearance is facilitated by CSF flowing into the perivascular spaces, only when we are asleep, is that because it would take the place of what usually flows from blood vessels to brain tissue: oxygen and glucose? In other words, is it limited to sleep-times because the brain is not so busy, and can get by with less oxygen and glucose?

2. Is the perivascular CSF-waste-clearance happening only in veins? Or do the spaces around arteries get filled as well? This question also arises from the oxygen/glucose question...

[cheerleader]

Hey 1eye:
1. The reason this only happens when we sleep is because the brain's inactivity is what allows fluid to flow through. Here's a paper that explains it in relationship to your glucose question. Might be worth it to purchase for more answers. I didn't ask that of Dr. Nedergaard, so I don't have answers for you, but I'm sure she does http://www.ncbi.nlm.nih.gov/pubmed/25947369

2. The waste clearance is only around veins. The meningeal artery may be involved in bringing lymph in, I don't know. These recent studies have only looked at how lymph exits---and that's around the veins. Here's a new blog post I wrote, with pictures, to describe the connection found. http://ccsviinms.blogspot.com/2015/06/p ... words.html

Here's a great video, new to this thread, from the University of Virginia Kipnis Lab, discussing this discovery, and their commitment to finding answers for people with MS. This lab is pretty freakin' great.
cheer

[cheerleader]

Great article in Maclean's Magazine today, on the discovery, with interview of Dr. Antoine Louveau

The discovery of a lymphatic system in the brain potentially overturns current thinking about diseases such as MS, he (Louveau) says: “It definitely could bring new light to the etiology of neurodegenerative diseases, which could shape treatment. Maybe by targeting those lymphatic vessels instead of targeting the immune system, per se, we may be able to ameliorate those diseases.” It’s a bold hope, one born of being able to see beyond medical dogma.

http://www.macleans.ca/society/science/ ... the-brain/


cheer

[cheerleader]

Wanted to explain how lymphatic vessels piggyback and drain through cerebral and extracranial veins, so I did it with pictures.
http://ccsviinms.blogspot.com/2015/06/p ... words.html

hope it helps explain this discovery--and the newly defined vascular connection to neurodegenerative diseases,
cheer

[Moragh]

Many of us go searching around the internet looking to better understand the roles and responsibilities of things. (well me anyway). With this new information I started searching around as I really didn't understand what the lymphatic system did.

I came across this site and found it very helpful in explaining the Immune/ lymphatic system - at least what's mapped. It also has sections on cardiovascular / nervous system & brain functions (nothing to do with MS) just what their jobs are. It helped me tie a few things together. Hope its okay to put the link here might help others like me understand a bit better.

Cheer thanks for posting your not talking to yourself.

http://www.innerbody.com/

[Scott1]

Hi Cheer,

You may find this paper from Chile of interest. Whilst not directly transferable to your description of your husbands condition there are segments that would fit others. http://www.tos-syndrome.com/LAST%20ONER ... 20M%20S%20(1%29.pdf
They take the CCSVI concept but apply it to thoracic outlet syndrome. Effectively a refinement of the area to target.

Regards

[cheerleader]

Thanks, Scott,
yes, we know TOS pretty well on the CCSVI forum, and CCSVI researchers do, too. We've had some good discussions on TIMS.
http://www.thisisms.com/forum/chronic-c ... 24724.html
http://www.thisisms.com/forum/chronic-c ... 18546.html
http://www.thisisms.com/forum/chronic-c ... 12121.html

Thanks for the link, Moragh. That's a great site! Sharing links is encouraged around here. Glad this discussion is helpful. ThisIsMS is a great place for back and forth, that's why it's more fun than just talking to ourselves.
I love the Kahn Academy for easy to understand, scientific explanations. My son got me hooked on these videos. Here's one on the lymph system I found very helpful.
https://www.khanacademy.org/test-prep/n ... move-fluid

And now we know that lymph is draining from the brain! Incredible discovery.
cheer

[Scott1]

Hi,

When I was in the midst of my attack last year I wrote a note on Sunday 28th September 2014 (http://www.thisisms.com/forum/regimens- ... 19-45.html) where I commented about the lymph system
"Here is a diagram of the system. (http://www.livescience.com/26983-lymphatic-system.html ) If I had to run my fingers over the front of me that felt affected it would follow the path of the green lines and include the spleen. Earlier it was so diffuse I couldn’t have made a distinction as I felt so overwhelmed but if you can see it that’s where I felt it."
Of course, we didn't know about this new connection at the time but the MRI's at that point of my brain looked like a snow storm there were so many white spots.

Regards

[Leonard]

Hi Cheer,

You are doing great! You don't talk to yourself, you talk to hundreds of people, often extremely motivated people.
With your constantly weaving stories and connections, you stimulate thinking, you provide a new prism for understanding, you can't imagine what this causes in smallest corners of this world.
Sometimes the reaction may be slow but just don't feel put off; in the background there is always this new society at work.

I found these interesting books:
The Starfish and the Spider, the unstoppable power of leaderless organisations by Brafman and Beckstrom and
Citizen Science: the underrated knowhow of the layman by Peter Finke (in German)

Because I worked in this area as a policy maker, I know there are some other good publications including on the total review of the intellectual property regime. You can't imagine what is all changing. You contribute by your great analyses! Please keep on doing the good work!

Leo

[cheerleader]

Scott--You were making the connection to lymph in the rest of your body--and now we know that system is connected to the brain. Very intuitive of you!

Thanks for the kind words, Leo. Appreciate the book recommendations. Will check them out! I just did a podcast with Dr. Jon Chung---which gives some more info on Jeff and my journey. Dr. Chung called me a "citizen scientist." That book must be where he got the title from!
http://www.healyourselfradio.com/post/1 ... entist-and

cheer

[Scott1]

Hi Cheer,
I wish someone had looked at me as something to measure at the time. It was a very uncomfortable place to be but I'm glad I wrote it down. We have a way of forgetting discomfort when it abates and I doubt I would have remembered it in such detail after the event. The lesson for me was it was very like the inflammation feedback loop we get with an ingrown toenail. A bit of pressure leads to swelling, the swelling creates more pressure which causes more swelling as the immune system responds by pumping the area with its "attack troops" who find nothing there but keep coming.
I guess the issue is not the immune response but the original event. The only answer at the stage I was at was intravenous prednisolone to calm the attack down. Gradually I have recovered but it was a big episode.
So I can see the logic in taking drugs that shift the immune response from Th1 to Th2 but can see they must ultimately fail as they don't address the cause. Our "Toenail" just keeps growing.
I can also the logic for interferon's if they stimulate the immune system to attack possible causes of inflammation but can see they will have little effectiveness if the immune system cannot see the cause.
It seems to me that the original event eventually overrides everything. It could be viral or metabolic or physical or a combination. My "Toenail" is probably EBV with a supporting cast of infections and bad luck. Jeffs may be more physical with its own supporting cast. Others may have infection raging through them that constricts their blood vessels on top of existing narrowness. In each case we need to attack the cause but remain in a non inflammatory state.
Regards

[cheerleader]

Scott--absolutely! Calming the body's disregulated and over-reactive immune response/inflammation, while still allowing the immune cells to do their repair work in the CNS will be the future goal of MS treatments. And it appears there is a link to the vasculature.

Here's a great new interview with Dr. Jonathan Kipnis from Public Radio Internation (PRI) on the lymphatic vessels his team has discovered.

“The immune link with so many neurological disorders is now obvious,” Kipnis says. “If the immune system is involved with those disorders, [then] the communication between the brain and the immune system is mediated by these vessels. We believe that they probably will be found to play a major role in most, if not all, neurological conditions where the immune system is involved.”

http://www.pri.org/stories/2015-07-04/s ... une-system

cheer

[1eye]

Ok, which is it?

Are these vessels in the brain really vessels, with inherent vessel walls, which are connected to the rest of the body's lymphatic system, or do they have "glymph" in them, and not much in common with the system outside the brain, etc.?

In other words, is this the same or a very similar system to that which is seen in mice, where glymph passes through spaces which are created ad-hoc (like during sleep) by brain shrinkage, increasing the spaces outside blood vessel walls?

Do these "glymphatic vessels" have vessel walls which contain the flow, or are they default "vessels" such as those seen in mice, with no inherent vessel walls, simply spaces, that on occasion (such as during sleep) are filled with (g)lymph, and as required, simply disappear so that brain tissue comes into more direct contact with blood vessel walls?

If there is something in humans that is not found in mice (like lymphatic vessel walls in human brains), then doesn't the murine brain differ so much from humans as to explain much of the failure of drugs which are tested with the obsolete EAE model?

I am getting excited about this, and not necessarily in a good way...

I have seen small film clips purporting to show T cells locomoting along the outside of blood vessel walls. They seem also to follow some trail of signalling molecules that actually takes them away from the bloodstream and towards brain tissue. The interaction between the lymphatic and immune systems in the brain may be exceedingly complex, determined by CSF/glymph as much as or more than what is in blood.

[cheerleader]

1eye---The vessels discovered by both Helsinki Un. and the University of Virginia are actual, real lymph vessels with enclosing vessel walls. These vessels line the meningeal layer and drain alongside cerebral veins. The mouse and human brains both contain actual vessels--and as inferred, probably ALL mammalian brains have lymph vessels in the meningeal layer.

The lymph cleansing system discovered by Dr. Nedergaard does not involve vessels inside cerebral brain tissue. It is a free-flowing wash of CSF and lymph fluid, facilitated by glial cells (thus the "glymphatic" name) and sleep. However, the theory is that these newly discovered vessels are used for drainage of this interstitial cleansing fluid. This theory needs further research. The interaction between the CSF, blood, lymphatic and immune system in the brain IS complex. We're at the beginning,

Dr. Schwartz has been publishing for 15 years on the fact that those circulating T reg cells you mention are there for a purpose: to facilitate cognition, neuroplasticity and healing in the brain. We ablate the immune system in the brain at our peril.
http://ccsviinms.blogspot.com/2015/06/d ... right.html
cheer