Brain lymphatics are like buses wait fifty years and two papers come all in a short space of time

B
Aspelund A, Antila S, Proulx ST, Karlsen TV, Karaman S, Detmar M, Wiig H, Alitalo K. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med. 2015 . pii: jem.20142290. [Epub ahead of print]

The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease.

So here we have another paper in a similar vein to the recent paper in Nature. Louveau et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015 Jun 1. doi: 10.1038/nature14432. That was discussed previously (click


It was originally proposed that the brain had no lymphatics so that antigens couldn’t be taken to lymph glands to start an immune response. However, we have known so many years that this is not quite right because we could see brain antigens in lymph glands. Lymphatic vessels were proposed and have been found and will contribute to the glymphatic system of the brain.


Lymphatic vessels are collapsed structures between the meninges (outside of cover of the brain), and if one does not know how to look, they cannot be found. These two groups worked out how to look.


This has nothing to do with CCSVI, which is going round the MS conspiracy theory circuit, and if textbooks need to be updated to include these discoveries they are not going to talking about CCSVI. 


Furthermore the brain still has relative immune privileged as the experimental results are not going to be wrong, just the explanation needs addressing and it is still clear that the brain has many features that are down regulated when it comes to immune function.


However, one has to be clear that once the immune response has become activated against brain antigens there is no immune privilege in the brain

The question is; if MS does contain an element of autoimmunity,where does it start in the brain (inside-out) or the lymph glands (outside-in)? 


The likely place has always been in the lymph glands because this is the place where the body has evolved structures for that to happen and even if the first event happens in the brain then the targets will be transported into the lymph glands for this to happen.    


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MouseDoctor

56 comments

  • Your opinion "This has nothing to do with CCSVI, which is going round the MS conspiracy theory circuit, and if textbooks need to be updated to include these discoveries they are not going to talking about CCSVI. " doesn't fit with the understanding that the CSF flow is created by the pulsations of blood into and out of the CNS.
    If the CSF is not flowing 'sufficiently' then the lymphatic system who not be working 'sufficiently'.
    Same for awareness that if the blood flow through the brain is insufficient the supply of oxygen, as one example, is insufficient and symptoms occur.
    If the other tasks of blood flow and the tasks of lymphatic system are insufficient then one would 'assume' that symptoms will occur, become chronic and that a cascade of illness will be evident.
    Most if not all degenerative diseases involving the CNS are cascades that have an unknown origin, you statement that CCSVI will not be included in the textbook re-think and rewrite appears biased and not for Scientific reasons.
    Is this type of comment helpful to PwMS?

    • I look forward to posts that include the new understands from an unbiased prospective, we, PwMS, all need to be heard and treated to gain some Quality of Life, rather than to be treated as mindless sources of income for the Pharma Industry.
      Regards Nigel 😉

  • I just read your comment on Joan Beal's blog http://ccsviinms.blogspot.ca/2015/06/rewrite-textbooks.html?showComment=1435600655398#c6122659262627698080 where you stated: "Have to say two wrongs do not make a right and these discoveries have nothing to do with CCSVI"

    Have you read her reply?: "Well goodness! A pop in! Actually, I have spoken with both of the lead scientists at the Nedergaard Lab and the Kipness Lab here in the US, and they disagree with that assessment. They see how this newly discovered (g)lymphatic drainage system relies on the intra and extra cranial veins for drainage, and they will be studying how stenosis and venous reflux may be impacting the brain's removal of CSF and lymph, and impacting ALL neurovascular disease. This discovery is bigger than MS, bigger than EAE in mice and I'll continue to blog about it. Two wrongs have injured people with MS for too many years, and I intend to make sure that doesn't continue."

    She also included several links to statements that disagree with you so I guess you'll not post this
    since you're not involved in this research and your blog has "an emphasis on the research we are involved in. A major reason for maintain the Blog is to thank the funders of our research. Funders encourage us to engage with the general public, people with MS and their families and other people with an interest in MS. We believe you have the right to know what we are spending your research money on!"

    I know you wouldn't want to make waves with your funders!

    • It is obvious that fluid exit relates to fluid input….what has this got to do with whether are blocked veins or not. I have spoken to Jonathan Kipness so what?

      The claim "This discovery is bigger than MS….." seems to me to show the ability to assimilate information is dislorted.

    • Re. Bigger than MS.

      A quote from Kipnis' Abstract:
      'The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.'

      Why does that demonstrate her 'ability to assimilate information is distorted'? MS unfortunately not the only neurodegenerative disease.

    • I am ace….I can write this in an abstract…you can choose to agree or ignore, likewise I can chose to assimilate or ignore or which parts to assimilate what appears in Nature and how they big up stories…

      However let's try an get it from the horses mouth. I have asked Jonathan Kipnis if he would like to do a guest post and specifically I have asked him (in a no leading way) to comment on how this discovery lends support to the CCSVI concept…..lets see if he accepts.

    • Jonathan has agreed to do a guest point on CNS lymphatics sometime in the future
      however

      I said " I would also be interested how you feel it supports the CCSVI hypothesis"

      The Horse's Mouth…. OK Jony said (Thu, 2 Jul 2015 23:20:46 +0300)

      "With regards to CCSVI I am completely agnostic since I am not sure I understand it well enough. I definitely cannot claim for any connection to the lymphatic vessels simply because we have not done any of these experiments"

      This seems a sensible answer, I won't go back to mention this on Joan's Blog as best let sleeping dogs lie. Maybe this can be the end to this interlude

    • Interesting reply and it could be the standard game of pedantics males play.
      If you ask the question, is there a connection between blood flow, CSF flow and lymphatic flow to Jonathan Kipnis you might find that because you are writing rather than verbally having a two way conversation that you receive clarifications.
      Any question can be framed in writing to receive an answer that you prefer, rather than an open question stating that there is a purpose for the communication which will frame the answer unbiasedly!
      Another question that would be purposeful for this forum would be to clarify the relationship of the 'glymphatic system' and the CSF wastes and immune system cycling. 😉

    • Kettle an black spring to mind here
      Frankly I am not interested in a one or two way conversation on this subject' on ccsvi and ask about the glymphatic system' and the CSF wastes and immune system cycling and again the conversation will go no where near CCSVI simple as that, end of story.

  • hard to take anyone serious who does not give their name. Sniper attacts have no place if ones objective is objective science.

  • Having a PhD doesn't invalidate MD's right to his own opinion. That's true regardless of whether he gives you his real name or not. He obviously disagrees with you. I'm on the fence on the whole affair, but I'd prefer to hear people's honest opinions on the matter, regardless of their views.

    And insisting that someone give you personally identifiable information simply so that they can have a right to their opinion is cracked. Especially on a board where 95% of the folks who post are either 'anon', or using some type of pseudonym.

  • Interesting article about this discovery in a Canadian news magazine.

    http://www.macleans.ca/society/science/are-we-on-the-cusp-of-a-revolution-on-how-we-understand-the-brain/

    The discovery of a lymphatic system in the brain potentially overturns current thinking about diseases such as MS, he 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.”
    Is there any hope you'll ever be able to see beyond medical dogma?

    • If you target the vessels you stop fluid outflow anyone who has had lymph glands removed when cancer is suspected may tell you lymphoedema (swelling) can occur. pu dont want brain swelling.

      The story is very interesting but your headline from the link is media rubbish "cusp of a revolution indeed". In UK Macleans is a toothpaste.

      Targeting the immune system works as shown by the effect of ocreluzimab in todays news. However this work brought to my attention the glymphatics and how this clears/flushes the brain whilst you sleep is interesting.

      We will have to agree to disagree as you have your views and i suspect they are not going to change.

      However to accuse me of being blinkered to medical dogma means you do not know who we are or maybe you are a part time visitor.

    • i have no idea of who you are as you call yourself the "mouse doctor". I have seen "snipper attacks" on other sites from you. Not helpful. If you have a valid arguments then identify yourself and make them. Making snide comments ..not helpful.

    • Dear Lori, I guess we don't see eye to eye and do not remember getting your emails but threads with links and insults generally end up in the bin

    • Dear Flo
      MouseDoctor here.

      You call yourself Flo but I have no idea who you are. It is pretty easy to be anyone you want to be in web land

      You have seen sniper attacks on other sites…you mean I left a comment when following the link left from one of the posters on this site that site happens to be our friend Joan….We bought her single for ProfG as she wrote a nice little piece about him.
      Yes I often check out the links put in posts because they can be advertising posts and send you off to some choice places.

      I think I wrote "two wrongs do not make a right" which is a proverb that any one can say
      and then that the presence of lymphatic vessels in the brain has nothing to do with CCSVI again anyone can say that. If I said toenails have nothing to do with CCSVI would this be a problem?

      Unfortunately it seems to me that this creates a portal that brings the Trolls out (p.s. I am not calling you a troll but our spam box is littered with some choice comments rom people who are

    • Are you saying that you don't use your real names because you don't want to get harrassed by Trolls?

    • In North America you have the latest bit of animal vivisection on the news at 6. But you have a few nutters that bomb abortion clinics. In the UK it is the other way round.

      In the UK people love their furry friends and there are extremists.

      http://www.understandinganimalresearch.org.uk/policy/animal-rights-extremism/the-early-history-of-animal-rights-extremism/

      This has made many/most people who work with animals to very, very private and cautious.

      I knew people who would have their car checked every day for Bombs and regularly got death threats. They have now retired.

      The Government wants us to be more open and have targeted their cash flow to stop their activities, but there are still nutters out there…largely after people working with monkies cats and dogs. However it takes about 5 minutes with Dr Google and pubmed to find out what people are up to.

    • At least Flo isn't trying to pass himself/herself off as an expert in research. What's wrong with asking for accreditation from someone who spouts "knowledge"?

    • Lori (at 5.20pm) it's quite easy to find information about MD1's expertise on this blog. Try the About us section to start with. Sorry MD but you must be hiding in plain sight from the 'animal rights activists'. Mind you, it seems in the case of Lori, it works as a strategy ;(. Really Lori you don't need to be so insulting, it does your cause no favours.

    • "What's wrong with asking for accreditation from someone who spouts "knowledge"?"

      I suspect we could supply all the accreditation requested but it wouldn't make a blind bit of difference if our opinion should diverges from the CCSVI party line.
      Now let's move on shall we?

  • I was just sayin' that from Kipnis' point of view, it seems to be about more than MS….

    I hope you were more polite in your email, as I think it would be, err, ace… if he did a guest post 🙂

  • Once again, I see you have not posted my reply to your comment of Wednesday, July 01, 2015 3:31:00 a.m.–let's say because I included a link (although you did post one of my previous comments that included a link so you must have taken something I said as an insult). I'll try again.

    You are right that my views won't change about this particular issue because I am walking proof that venous angioplasty improved many symptoms of mine that had been attributed to Multiple Sclerosis, when NOTHING ELSE EVER DID! I KNOW you cannot name any drug that can help, or even "appear" to help, symptoms for someone with PROGRESSIVE MS, because there is nothing on the market yet.

    I have medical documentation of my improvements at the UBC MS Clinic in Canada–one of the sites of the pan-Canadian CCSVI treatment trial. I am a member of the BC CCSVI Registry that disclosed interim results showing that half of the people had good results. The neurologist in charge of the Registry and trial said that these results were just "impressions" but I have written evidence that they requested medical info from the patients' doctors and I have a copy of my report that says "SIGNIFICANT" improvement. He also felt strongly enough that "something" was happening that an actual TREATMENT trial was warranted. At least he cares enough to investigate further.

    I don't think "targeting" the lymphatic vessels is the main point of this discovery. This discovery shows that the brain actually does drain Central Nervous System fluid via lymphatic vessels to veins–to quote one of the Helsinki researchers–“This incredible finding completely changes our understanding of how the brain is cleared of excess fluid, and gives a chance to look at brain diseases from a completely new angle.” . The purpose of venous angioplasty for CCSVI is to remove occlusions in veins that don't allow proper drainage so I believe it is related to CCSVI.

    • I did not delete your post…if you use the TROLL FONT i.e. capitals

      You cannot name any drug that can help symptoms for someone with PROGRESSIVE MS.

      How about baclofen, gabapentaine, viagra, fluoxetine, tizanidine etc. all rugs that help symptoms

      You didn't really mean what you wrote

      "You cannot name any drug that can help, or even "appear" to help PROGRESSIVE MS"
      How about simvastatin?

      As to your recovery I am very happy that this occurred and appreciate that youtube has many vidoes but this is not the place for them as they have insufficient provenence

      "The purpose of venous angioplasty for CCSVI is to remove occlusions in veins that don't allow proper drainage so I believe it is related to CCSVI"

      The blockage of veins is contentious

    • Lori
      You're obviously a CCSVI evangelist. Please don't be offended if not all comments in favour of CCSVI are posted as this has led to the ruination of other MS sites. We think the whole concept is bogus, recent work seems to confirm this and we don't want pwMS wasting their money on an unproven procedure.

    • Sorry, I meant to say that you cannot name any of the so-called "disease-modifying drugs" that can claim any symptom relief. They can't. I received a quote from a previously naysaying neurologist who has the fortitude to admit this is justification of the concept of CCSVI–
      "These are two important scientific observations, demonstrating what neuroimmunologists argued for some time. In fact, previous studies had suggested the presence of a lymphatic drainage from the central nervous system. These studies complete the picture and provide further support to the theory, more and more concrete, the autoimmune pathogenesis of MS. And, in fact, more clear how brain antigens can get in lymphoid organs and, in these, initiate an autoimmune response.
      Quite an achievement for someone like myself, who has always believed and supported that multiple sclerosis is an inflammatory autoimmune disease.
      I also think that this study puts the word END at pathogenic hypothesis supported by Dr. Zamboni."

      At least some people can admit when they are wrong!

    • Unless I'm missing something, that quote does the exact opposite of validating the Zamboni hypothesis. It's clear whoever said it is saying it confirms the autoimmune hypothesis of MS.
      Hope that clears things up 😉

    • Not that I'm a scientist but that's my understanding too. Really had more than enough of hearing about CCVI. The evangelical and sometimes quite nasty sarcastic remarks from the supporters of it, do it no favours. Please go somewhere else.

    • I wanted to see if you actually read posts–that was an example of how naysayers are trying to "spin" this discovery–thought it might have been you!–no name given by the speaker, either, so once again, no credibility. I believe the words of the researchers who made this discovery–their names are on it and they can be seen on youtube talking about it. I'll listen to someone who knows what they are talking about!

    • Lori @5.39pm, frankly I feel it is you that is not reading the comments, or rather just hearing what fits with you world view and denigrating the I hear loud and clear that you feel CCSI has done a miraculous job for you, I'm glad for you but just because I'm not going to follow this path, doesn't mean I need to hear you screaming (capitals in your comments), or insulting others who hold different opinions. The paranoia (in the above comment) and attempted heavy-handed sarcasm in your comments really seems a tad bonkers to me.

    • "I'll listen to someone who knows what they are talking about!"
      All the evidence suggests you'll only listen to those who agree with your opinion.

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