The 12th Invest in ME Research Conference June, 2017, Part 2
MEMum presents the second article in a series of three about the recent 12th Invest In ME International Conference (IIMEC12) in London.
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Second Study Shows Lymphatic System in The Brain

Discussion in 'Other Health News and Research' started by Never Give Up, Jun 17, 2015.

  1. Never Give Up

    Never Give Up Collecting improvements, until there's a cure.

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    The Journal of Experimental Medicine just published this! Note the submission and publication dates at the end.

    http://jem.rupress.org/content/early/2015/06/09/jem.20142290.short

    A Dural Lymphatic Vascular System that Drains Brain Interstitial Fluid and Macromolecules

    Aleksanteri Aspelund,1,2 Salli Antila,1,2 Steven T. Proulx,3 Tine Veronica Karlsen,4 Sinem Karaman,3 Michael Detmar,3 Helge Wiig,4 and Kari Alitalo1,2

    ABSTRACT

    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.

    Submitted: 8 December 2014
    Accepted: 4 June 2015
     
    leela, JaimeS, SOC and 10 others like this.
  2. Jonathan Edwards

    Jonathan Edwards Senior Member

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    Thanks for flagging tht. It seems to clarify some of the queries we discussed on the other thread.

    It looks as if immunological drainage from brain may not be through the main reservoir of CSF as such, which may mean that measuring CSF levels of cytokines etc may not be telling us about events in the brain very reliably. It may indicate events in subarachnoid space. The maintenance of a positive hydrostatic pressure despite the presence of exit routes could be explained by 'raspberry valves' - these are exits that have no rigidity so collapse down under the pressure that should be feeding them thereby blocking themselves off. A small exit flow might be maintained by arterial pulsation briefly sucking the exit open and then shutting it again so that individual shots of fluid are expelled - i.e. the system you have in an optic measure on a whiskey bottle. You have to keep reversing the pressure and fluid only comes out in small shots.
     
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  3. Bob

    Bob

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    That's an interesting observation. From reading research literature, I think it's often taken for granted that the CSF is linked to the brain in some way. I'm not sure why. Perhaps people assume there's at least an indirect link, because the fluids are similar? Or perhaps similar infections are often found on the brain and in the CSF?

    Shouldn't it be quite easy to find out exactly where brain fluids and CSF fluids drain off to, at least in a mouse model? I would have thought that they could simply inject the brain and CSF with separate (i.e. radioactive) markers and then place the subject in a scanner.

    If they can discover exactly where the brain fluids drain to, then the next step would be to see if it's easy to extract the drainage fluids for examination in research studies, thus obtaining brain fluids while avoiding invasive brain procedures.

    (Apologies if this has all been discussed before.)
     
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  4. Never Give Up

    Never Give Up Collecting improvements, until there's a cure.

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    Here's a write up from the University of Helsinki:

    http://www.med.helsinki.fi/english/news/2015/20150615_aivoimut.html

    Read full article here.
     
    Last edited by a moderator: Jun 18, 2015
    Bob likes this.
  5. Jonathan Edwards

    Jonathan Edwards Senior Member

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    Studying fluid dynamic physiology is far from straightforward because there are different components of diffusion and convection involved at all different molecular and cellular levels. It should certainly be possible to follow tracers injected into branches of cerebral arteries at least in large mammals. Mice might be tricky and of course the relation of diffusion to convection will be different in mice and humans because of size factors. You also have to distinguish convective flow across boundaries from convective flow within chambers or compartments. Physiologists routinely get the analysis wrong for fluid dynamics - which is where Rod Levick and I had to do work to sort out what really goes on inside joints.

    So far my impression is that the most likely message from this new stuff is that antigen presenting immune cells would be able to traffic back to lymph nodes from brain tissue without getting lost washing about in the free CSF compartment - which makes a lot of sense. I am a bit doubtful that ideas on protein clearnace would change much.
     
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  6. Jeckylberry

    Jeckylberry Senior Member

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  7. Little Bluestem

    Little Bluestem Senescent on the Illinois Prairie ❀❤✿Ƹ̵̡Ӝ̵̨̄Ʒ✿❤❀

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    Those unknown unknowns surprise people.
     
  8. Jeckylberry

    Jeckylberry Senior Member

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    Don't they! They used to believe they had mapped the body when they thought that the heart was fuelled by fire and that the babies grew entirely from the sperm, that bad air was the cause of cholera and that you blow smoke up the backside to revive a drowned person. Every generation has been guilty of this self same arrogance. When will they learn to approach it with the mind of a scientist and not a doctor?
     

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