13 ms·

The brain's waste clearing lymphatic system shown in people for first time

316 points by SubiculumCode 2y ago

elric 2y ago
It's taken 12 years to get from "this stuff exists in mice" to "we now know it actually exists in humans and is not vestigial". That seems like a long time. People get brain MRIs with contrast all the time, is there any reason why this never showed up? Because no one was looking? Or because it's a slow mechanism?
- jhrmnn 2y ago
  Looking up “brain MRI with contrast”, the biggest difference seems to be that in a regular MRI the contrast goes to the blood, but here it goes straight to the brain cerebrospinal fluid. You need open brain for that, so indeed doesn’t seem trivial.
  - elric 2y ago
    Cerebrospinal fluid is produced in the brain, I would imagine that the contrast would end up in newly produced fluid as well, but maybe that assumption is wrong.
    - sithadmin 2y ago
      Even assuming that the contrast could show up in newly excreted CSF (maybe, maybe not), MRI contrast elimination half lives are very short (mostly all under ~2 hrs, excepting cases like renal dysfunction), and cerebrospinal fluid doesn’t replenish particularly quickly.
    - physPop 2y ago
      Unfortunately no, that is not how the contrast agent gets around. Most Gd agents are huge and don’t leak out of the vasculature unless there is a disruption (tumour etc).
- NeuroCoder 2y ago
  Two things: 1. Blood brain barrier and CSF should be separate for all but tiny molecules. It's why CT angiograms are able to visualize distinct vessels. So it is pretty hard to directly interact with this sort of thing in vivo 2. A good chunk of the neuro community have been operating under the assumption that some of those mouse model findings are mechanisms in humans too. Since we couldn't easily prove it, people used a bunch of next best tools with fancy imaging that demonstrated it was very likely. On top of furter proof, this sort of study allows us to begin pinpointing exactly how close our next best tools are at estimating in vivo processes without opening up the head.
- jb1991 2y ago
  The main reason is because 12 years ago we didn't have ChatGPT to tell the researchers the answer.
- rozab 2y ago
  They injected a dye into the cerebrospinal fluid to confirm the pattern of diffusion into the brain. I imagine this procedure would have to be confirmed safe in humans first. Also they needed subjects who already happened to be undergoing a specific type of brain surgery.
- physPop 2y ago
  Its because we don’t normally inject Gad in CSF. Its kind of wild west to even do so, and these researchers were able to identify this unique dataset and ask some interesting questions.
PaulKeeble 2y ago
There have been a couple of papers [1] that can induce this process while awake using particular image patterns as confirmed in an MRI. I think the NIH confirmation is running behind in the science, independent research is quite a bit ahead of them. I came across the paper on this last year and implemented a very simple page with the parameters they used [2]. There is a number of disease models that show reduced or no glymphatic clearance and as such these people need treatments to clear out their brains and these image routines seem to help. A lot of people find this pattern extremely taxing to watch especially for the recommended number of cycles, you can feel the effect on the brain its hard to describe the sensation its a bit numbing and the image has the sensation of changing as the cycle runs like its a visual trick. You might get left feeling like you have been clubbed over the head the first time. I find it interesting this is one aspect of disease research I am looking into and is related to Long Covid and ME/CFS. [1] https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002035 https://journals.plos.org/plosbiology/article?id=10.1371/jou... [2] https://www.paulkeeble.co.uk/posts/cff/ https://www.paulkeeble.co.uk/posts/cff/
- kenjackson 2y ago
  This is fascinating. Curious, could seizures caused by strobe light be related to the effects of draining of this fluid?
  - khafra 2y ago
    From the paper, it seems like that the blood flow changes and the seizures are both caused by the increased processing load in the visual cortex; with the seizures also resulting from some faulty wiring in localizing that increased load to only the visual cortex. So, more like A->B and A->C instead of A->B->C. But I'd bet this visual stimuli is even more effective at causing seizures in vulnerable people than an unfortunate pokemon episode.
- mikewarot 2y ago
  Holy cow.... that's really rough, you weren't kidding. This is the closest I've ever felt to being a Borg.
- 2y ago
sharpshadow 2y ago
“Other studies have suggested that the glymphatic system may be most active during sleep.” Not only that but also the right sleeping position is relevant here. I don’t recall the scientist but he studied primates and their natural sleeping position, exactly this position also opens up the channels for the cerebrospinal fluid to flush the accumulated brain waste.
- lazypenguin 2y ago
  Do you recall which position?
  - mfro 2y ago
    > Glymphatic transport is most efficient in the right lateral sleeping position https://pmc.ncbi.nlm.nih.gov/articles/PMC7698404/ https://pmc.ncbi.nlm.nih.gov/articles/PMC7698404/ Section 3.4.3
    - sharpshadow 2y ago
      Yes that’s the position. Good to see it verified in the study. Having a partner and sleeping in the same bed can lead to alterations from the optimal sleeping position, especially sleeping on the back is not good. Sleeping on the back is also one of the main causes of snoring, which often occurs in people which have a big belly and can’t really sleep lateralish anymore. Sleep quality is important too and one big factor is not to go to sleep with a full stomach. Sleep quality will suffer because of the active digestion which probably will not let the glymphatic transport do it’s job properly. Also good to know that “…low doses of alcohol (0.5 g/kg) increased glymphatic clearance…”.
      - teagoat 2y ago
        Is increased glymphatic clearance good or bad?
        earslap 2y ago
boringg 2y ago
Interesting - whats the frequency - response hypothesis? I don't think you would want to do lymphatic drainage everyday unless you had a problem with your system (?)
canadiantim 2y ago
Really shows the slow slow slow glacial pace of science and how fragmented the information distribution mechanisms are…
- knodi 2y ago
  Or the brain is high complex organ and full of MANY known and unknown functions which meet a specific or general need. Don't forget, it took us 100k years as human to get here, our current understanding of brain. you're being a little harsh here.
s5300 2y ago
[dead]

316 points by SubiculumCode 2y ago

It's taken 12 years to get from "this stuff exists in mice" to "we now know it actually exists in humans and is not vestigial". That seems like a long time. People get brain MRIs with contrast all the time, is there any reason why this never showed up? Because no one was looking? Or because it's a slow mechanism?

jhrmnn 2y ago
Looking up “brain MRI with contrast”, the biggest difference seems to be that in a regular MRI the contrast goes to the blood, but here it goes straight to the brain cerebrospinal fluid. You need open brain for that, so indeed doesn’t seem trivial.
- elric 2y ago
  Cerebrospinal fluid is produced in the brain, I would imagine that the contrast would end up in newly produced fluid as well, but maybe that assumption is wrong.
  - sithadmin 2y ago
    Even assuming that the contrast could show up in newly excreted CSF (maybe, maybe not), MRI contrast elimination half lives are very short (mostly all under ~2 hrs, excepting cases like renal dysfunction), and cerebrospinal fluid doesn’t replenish particularly quickly.
  - physPop 2y ago
    Unfortunately no, that is not how the contrast agent gets around. Most Gd agents are huge and don’t leak out of the vasculature unless there is a disruption (tumour etc).
NeuroCoder 2y ago
Two things: 1. Blood brain barrier and CSF should be separate for all but tiny molecules. It's why CT angiograms are able to visualize distinct vessels. So it is pretty hard to directly interact with this sort of thing in vivo 2. A good chunk of the neuro community have been operating under the assumption that some of those mouse model findings are mechanisms in humans too. Since we couldn't easily prove it, people used a bunch of next best tools with fancy imaging that demonstrated it was very likely. On top of furter proof, this sort of study allows us to begin pinpointing exactly how close our next best tools are at estimating in vivo processes without opening up the head.
jb1991 2y ago
The main reason is because 12 years ago we didn't have ChatGPT to tell the researchers the answer.
rozab 2y ago
They injected a dye into the cerebrospinal fluid to confirm the pattern of diffusion into the brain. I imagine this procedure would have to be confirmed safe in humans first. Also they needed subjects who already happened to be undergoing a specific type of brain surgery.
physPop 2y ago
Its because we don’t normally inject Gad in CSF. Its kind of wild west to even do so, and these researchers were able to identify this unique dataset and ask some interesting questions.

PaulKeeble 2y ago

There have been a couple of papers [1] that can induce this process while awake using particular image patterns as confirmed in an MRI. I think the NIH confirmation is running behind in the science, independent research is quite a bit ahead of them. I came across the paper on this last year and implemented a very simple page with the parameters they used [2]. There is a number of disease models that show reduced or no glymphatic clearance and as such these people need treatments to clear out their brains and these image routines seem to help. A lot of people find this pattern extremely taxing to watch especially for the recommended number of cycles, you can feel the effect on the brain its hard to describe the sensation its a bit numbing and the image has the sensation of changing as the cycle runs like its a visual trick. You might get left feeling like you have been clubbed over the head the first time. I find it interesting this is one aspect of disease research I am looking into and is related to Long Covid and ME/CFS. [1] https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002035 https://journals.plos.org/plosbiology/article?id=10.1371/jou... [2] https://www.paulkeeble.co.uk/posts/cff/ https://www.paulkeeble.co.uk/posts/cff/

kenjackson 2y ago
This is fascinating. Curious, could seizures caused by strobe light be related to the effects of draining of this fluid?
- khafra 2y ago
  From the paper, it seems like that the blood flow changes and the seizures are both caused by the increased processing load in the visual cortex; with the seizures also resulting from some faulty wiring in localizing that increased load to only the visual cortex. So, more like A->B and A->C instead of A->B->C. But I'd bet this visual stimuli is even more effective at causing seizures in vulnerable people than an unfortunate pokemon episode.
mikewarot 2y ago
Holy cow.... that's really rough, you weren't kidding. This is the closest I've ever felt to being a Borg.
2y ago

sharpshadow 2y ago

“Other studies have suggested that the glymphatic system may be most active during sleep.” Not only that but also the right sleeping position is relevant here. I don’t recall the scientist but he studied primates and their natural sleeping position, exactly this position also opens up the channels for the cerebrospinal fluid to flush the accumulated brain waste.

lazypenguin 2y ago
Do you recall which position?
- mfro 2y ago
  > Glymphatic transport is most efficient in the right lateral sleeping position https://pmc.ncbi.nlm.nih.gov/articles/PMC7698404/ https://pmc.ncbi.nlm.nih.gov/articles/PMC7698404/ Section 3.4.3
  - sharpshadow 2y ago
    Yes that’s the position. Good to see it verified in the study. Having a partner and sleeping in the same bed can lead to alterations from the optimal sleeping position, especially sleeping on the back is not good. Sleeping on the back is also one of the main causes of snoring, which often occurs in people which have a big belly and can’t really sleep lateralish anymore. Sleep quality is important too and one big factor is not to go to sleep with a full stomach. Sleep quality will suffer because of the active digestion which probably will not let the glymphatic transport do it’s job properly. Also good to know that “…low doses of alcohol (0.5 g/kg) increased glymphatic clearance…”.
    - teagoat 2y ago
      Is increased glymphatic clearance good or bad?
      - earslap 2y ago

boringg 2y ago

Interesting - whats the frequency - response hypothesis? I don't think you would want to do lymphatic drainage everyday unless you had a problem with your system (?)

canadiantim 2y ago

Really shows the slow slow slow glacial pace of science and how fragmented the information distribution mechanisms are…

knodi 2y ago
Or the brain is high complex organ and full of MANY known and unknown functions which meet a specific or general need. Don't forget, it took us 100k years as human to get here, our current understanding of brain. you're being a little harsh here.

s5300 2y ago

[dead]