CNS lymph vessels found. Brain is not immune-privileged

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cheerleader
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CNS lymph vessels found. Brain is not immune-privileged

Post by cheerleader » Mon Jun 15, 2015 9:03 am

(edit) New discovery from 2 separate universities is changing medical textbooks and MS research.
The brain is not immune-privileged, as postulated for decades;
Immune cells and lymphatic vessels are part of the brain's circulation, and rely on venous flow for drainage.
Animal model has been confirmed in autopsied human tissue.


New article from Cosmos Magazine which interviewed Dr. Kipnis (discoverer of lymphatic vessels in brain) and he stated that his team is now studying how inefficient brain drainage affects diseases like MS.
Generations of medical students have been taught the mammalian brain has no connection to the lymphatic system, to help keep the brain isolated and protected from infection. Louveau’s discovery will force a rewrite of anatomy textbooks, and could change the way researchers treat neurological diseases from Alzheimer’s to multiple sclerosis.

The researchers think they have also found similar lymphatic vessel structures in human brain samples, which may provide a fresh angle for neurological disease treatment. In multiple sclerosis, immune cells breach the central nervous system and attack the neurons’ insulating layers of myelin. And in Alzheimer’s disease, cell death is accompanied by protein clumping between neurons. Kipnis speculates that inefficient brain drainage could play a role in these conditions. His team is now looking into how the vessels differ in the brain of patients with brain diseases.

Back in 1998, Michal Schwartz, immunologist at Israel’s Weizmann Institute, was the first to suggest the immune system and the brain are in close dialogue. She’s pleased with the finding but not surprised by it.
https://cosmosmagazine.com/life-science ... your-brain

I wrote a blog post on Dr. Michal Schwartz June 9th. Was happy to see Cosmos Magazine followed the same trail.
http://ccsviinms.blogspot.com/2015/06/d ... right.html

interesting times,
cheer
Last edited by cheerleader on Sat Jun 20, 2015 7:11 am, edited 2 times in total.
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Re: NEW: Brain damage from bad drainage

Post by cheerleader » Thu Jun 18, 2015 9:16 am

Confirmation of University of Virginia finding comes from Helsinki University!
http://m.jem.rupress.org/content/early/ ... 2290.short

The brain has lymph vessels which run through the venous system and drain into the jugulars.
The brain has a previously unseen immune system dependent on lymphatics.

Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease.


this is the biggest paradigm change in understanding immune cells in the brain in 100 years, really surprised there's not more discussion.

thoughts?

cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com

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Re: CNS lymph vessels found, confirmed by Helsinki Universit

Post by cheerleader » Fri Jun 19, 2015 1:21 pm

Well, guess I'll talk to myself :)
Maybe someone else is interested.

Here's a great article explaining what Helsinki found, independent of the University of Virginia.
Lymphatic circulation forms a network that covers almost the whole body and is especially important to the tissue clearance of fluids and macromolecules as well as for immune defense mechanisms. Until now, the central nervous system has been considered an immune-privileged organ devoid of lymphatic vasculature.

The discovery has raised several new questions concerning some fundamental brain functions and the mechanisms of brain diseases. Researchers find it highly possible that lymphatic clearance of the brain proves to be important in neuro-immunological diseases as well as in diseases characterized by the pathological accumulation of misfolded proteins or fluid into the brain parenchyma, for example in Alzheimer's disease, which affects tens of millions of people worldwide

The new findings revealed that the dura mater lymphatic system is important for the drainage of brain interstitial fluid, macromolecules, immune cells and cerebrospinal fluid.
http://www.eurekalert.org/pub_releases/ ... 061115.php

cheer
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Re: CNS lymph vessels found, confirmed by Helsinki Universit

Post by cheerleader » Fri Jun 19, 2015 3:28 pm

Here is Dr. Kipnis of the University of Virginia discussing this ground breaking research and how multiple sclerosis could be related to impairment of these vessels which carry immune cells in the brain.
5 minutes.


cheer
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Re: CNS lymph vessels found. Brain is not immune-privileged

Post by cheerleader » Sat Jun 20, 2015 7:15 am

Nature Reviews in Immunology -- "A Brain Drain"
Immunologists have long believed that the central nervous system (CNS) lacks lymphatic vessels and have struggled to understand how lymphocytes access and exit the brain. Louveau et al. now describe the existence of functional lymphatic vessels that run parallel to the dural sinuses of the meninges.
http://www.nature.com/nri/journal/vaop/ ... i3878.html
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Re: CNS lymph vessels found. Brain is not immune-privileged

Post by Leonard » Sat Jun 20, 2015 10:01 am

hi cheer,

please have a look at my last posting on http://www.thisisms.com/forum/general-d ... 8-705.html

it seems as if many things come together now, the virus, the epsilon toxin, the lymphe drainage..

leo

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Re: CNS lymph vessels found. Brain is not immune-privileged

Post by cheerleader » Sun Jun 21, 2015 11:10 am

RIght, Leo--
all important info on your thread!

I think that there is an opportunity for many plasmic particles, iron, viruses, bacteria, toxins to invade brain tissue when the lymphatic and venous drain isn't working correctly.

Dr. Zamboni focused on the iron deposition he saw due to permeable blood vessels in the brain, and likened it to venous disease in the legs---The Big Idea: Iron-dependent inflammation in venous disease and proposed parallels in multiple sclerosis http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1633548/
but if the brain's drainage system is "backed up", all sorts of things can get into brain tissue that don't belong there, (not just iron!) due to refluxive force and endothelial dysfunction, and the breaking of the blood brain barrier.

And now, on top of all this, we learn that the brain isn't immune privileged. The brain is like other organs (and the legs!) it has lymph vessels and needs immune cells for neuroprotection, stem cell regeneration and survellience. And lymph is drained from lymph vessels, through the venous sinus into jugular veins. Total paradigm change.

Makes me wonder how neuroimmunologists are going to react to this....they were quick to dismiss Zamboni, but this new research comes from their speciality. Neuroimmonolgy textbooks are being rewritten.

Hope you're doing well!
cheer/Joan
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Re: CNS lymph vessels found. Brain is not immune-privileged

Post by cheerleader » Mon Jun 22, 2015 10:57 am

What does immune privileged mean? Why is this a big deal?

We've had a 70 year theory on the brain over-turned this month---
the theory of immune privilege was invented to explain why immune cells didn't go after foreign tissue in experiments. That the blood brain barrier made a wall which was impenetrable. It's been thought that the only reason immune cells would be in the brain would be to fight infection, or in an inflammatory attack after a stroke, or in an "autoimmune" disease.

But this was wrong. EAE was developed during the same era---and these assumptions about the brain have lead to some seriously mistaken means of treating MS, and taken research in the wrong direction when looking for etiology.

These theories have created a 20 billion dollar a year industry.

Here's more:
http://ccsviinms.blogspot.com/2015/06/r ... books.html

cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
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Re: CNS lymph vessels found, confirmed by Helsinki Universit

Post by NHE » Mon Jun 22, 2015 5:13 pm

cheerleader wrote:Well, guess I'll talk to myself :)
Maybe someone else is interested.
No, I'm sure that there are many like myself that are reading your posts. I realize that this discovery is a paradigm changer and that all of the neuroscience textbooks will need to be rewritten. The question for me is where do we go from here in treating MS? I think we're still a long way from answering that.

NHE

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Re: CNS lymph vessels found, confirmed by Helsinki Universit

Post by CureOrBust » Tue Jun 23, 2015 1:45 am

cheerleader wrote:this is the biggest paradigm change in understanding immune cells in the brain in 100 years, really surprised there's not more discussion.

thoughts?
cheerleader wrote:Well, guess I'll talk to myself :)
Maybe someone else is interested.
I know for myself, similar to NHE I think (sorry if I am misdirecting your post), I have yet to see any research that actually links this finding to MS. Zamboni's original paper made a BIG impact as it was specifically on MS. At this stage its all theory with no actual link to MS; ie its still all potential.
cheerleader wrote:Dr. Zamboni focused on the iron deposition he saw due to permeable blood vessels in the brain, and likened it to venous disease in the legs---The Big Idea: Iron-dependent inflammation in venous disease and proposed parallels in multiple sclerosis
cheerleader wrote:Makes me wonder how neuroimmunologists are going to react to this....they were quick to dismiss Zamboni, but this new research comes from their speciality. Neuroimmonolgy textbooks are being rewritten.
The neuroimmunologists will still view Zamboni the same, publically, as he was (as you say) all about the veins and iron. A lot of your own posts before this finding where about hyperfusion and hypoxia. They may feel people are moving the goal posts, right into their field; ie out of this "vien nonsense".
NHE wrote:I realize that this discovery is a paradigm changer and that all of the neuroscience textbooks will need to be rewritten. The question for me is where do we go from here in treating MS? I think we're still a long way from answering that.
My interest will be peaked when they find that it definitely (may) have an effect on MS and if there would be any theory's on how they could correct/modify the behavior of these vessels to our advantage.

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Re: CNS lymph vessels found, confirmed by Helsinki Universit

Post by NHE » Tue Jun 23, 2015 2:01 am

CureOrBust wrote:
NHE wrote:I realize that this discovery is a paradigm changer and that all of the neuroscience textbooks will need to be rewritten. The question for me is where do we go from here in treating MS? I think we're still a long way from answering that.
My interest will be peaked when they find that it definitely (may) have an effect on MS and if there would be any theory's on how they could correct/modify the behavior of these vessels to our advantage.
We don't even know if these lymphatic vessels are dysfunctional in MS. From a neuroscience perspective, all we know is that the Earth isn't flat anymore. There are many more discoveries to follow from this work.

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Re: CNS lymph vessels found. Brain is not immune-privileged

Post by Leonard » Tue Jun 23, 2015 4:08 am

You are right. The biggest mistake we could now make is to believe that every thing is solved. We must not fall in that trap and keep our minds open.
The discovery is very important but it is only one tiny bit of a much bigger picture.

The central role of the gut in immunity, the direct link between the brain and the immune system, the co-evolution of the herpes virus and cellular immunity, toxic bacterial cell molecules and transportable proteins triggering intra-cellular events, the role of oxidative stress and cellular antioxidant mechanisms, there is an array of health issues that must be reconsidered. All will have their role to play in unravelling MS.

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Re: CNS lymph vessels found. Brain is not immune-privileged

Post by cheerleader » Tue Jun 23, 2015 9:09 am

Not saying "everything is solved."
Saying that 70 year old dogma has been reversed. The brain is connected to the peripheral lymphatic system.
The brain is not immune-privileged. And this means current MS treatments need to be re-evaluated.
Dr. Michal Schwartz has been publishing on this for two decades, and has asked researchers to study how immune cells functioned in the brain: as protective, regenerative, necessary for the brain's plasticity, and for inflammation resolution. But not many other researchers have responded, because the prevailing theories have served their ends.
For decades, several axioms have prevailed with respect to the relationships between the CNS and circulating immune cells. Specifically, immune cell entry was largely considered to be pathological or to mark the beginning of pathology within the brain. Moreover, local inflammation associated with neurodegenerative diseases such Alzheimer's disease or amyotrophic lateral sclerosis, were considered similar in their etiology to inflammatory diseases, such as remitting relapsing-multiple sclerosis. The ensuing confusion reflected a lack of awareness that the etiology of the disease as well as the origin of the immune cells determines the nature of the inflammatory response, and that inflammation resolution is an active cellular process.
http://www.jneurosci.org/content/33/45/17587.short

It was a student of hers at the Weizmann Institute --Dr. Jonathan Kipnis (a co-author on the paper linked above) who invented the technique necessary to discover the brain's lymphatic vessel vasculature. And their work was funded by the NIH, not pharma. In this interview he discusses the research, and that his lab needs money to keep going...

Kipnis and his colleagues found that vessels expressing markers of lymphatic vessels elsewhere in the body ran along the dural sinuses, drainage lines in the brain that collect outgoing blood and CSF, emptying these fluids into the jugular vein. They also found that the vessels contained immune cells.
http://www.the-scientist.com/?articles. ... ain-Drain/

And although Dr. Zamboni has yet to publish anything on the connection of his research to this discovery--it's only been a month, and he's been busy working with NASA in Houston---he has begun making presentations at medical conventions on the potential connection of a stenotic dural sinus/jugular vein to lymphatic drainage issues.

I'm really hopeful this discovery will lead to more insight,
cheer
Husband dx RRMS 3/07
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Re: CNS lymph vessels found. Brain is not immune-privileged

Post by Anonymoose » Tue Jun 23, 2015 10:33 am

I've not had the time to study up on any of this. I don't even have the simplest understanding of the lymphatic system, but I'm wondering about something...if this peripheral lymphatic system is what does all the immune work in the CNS and it drains into the bloodstream, how is it that we have oligoclonal bands that are unique to csf? Wouldn't some of the same immune cells drain into the bloodstream and show up on blood tests (I guess CSF drains into bloodstream too so I don't get why the bands don't show up in blood from that either). I'm sure there's an explanation...anyone have it?

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Re: CNS lymph vessels found. Brain is not immune-privileged

Post by Bethr » Tue Jun 23, 2015 3:12 pm

Anonymoose wrote: how is it that we have oligoclonal bands that are unique to csf? Wouldn't some of the same immune cells drain into the bloodstream and show up on blood tests
I thought OB's could show up in serum? Anyway, I'm following all this quite closely. It must be going to affect a lot of other theories and treatment methods. It's certainly opened my eyes, and I think the implications will be huge.

I'm off to massage my lymphatic system :-) apparently it doesn't flow like blood, you have to get it moving :lol:

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