"The Secrets of COVID `Brain Fog' are Starting to LIft" WIRED Jul 1, 2022

[Aerowallah]

https://www.wired.com/story/the-sec...re-starting-to-lift/?utm_source=pocket-newtab

 

[Hip]

This brain fog research by researchers Michelle Monje and Akiko Iwasaki sounds interesting. So excerpts:

It seems that in brain fog, specialized microglia in the white matter may have become permanently switched on:

“There’s a unique subpopulation of microglia in the white matter called axon tract microglia,” Monje says. These have a specific genetic signature, she continues, and “are exquisitely sensitive to a wide range of insults,” like inflammatory or toxic stimuli.

In response to these stimuli, microglia can become perpetually reactive. One consequence is that they can begin eating away at needed neurons or other brain cells, which further disrupts the brain’s homeostasis. In the case of Covid-19, the scientists found that this reactivity persisted even at seven weeks after infection.

The factor that is switching on these microglia appears to be CCL11:

To figure out what exactly caused the microglia to become reactive, the researchers looked for the cytokines that had reached elevated levels. Specifically, Anthony Fernandez Castaneda, a postdoctoral researcher in Monje’s laboratory and a study coauthor, found CCL11—a factor that can decrease the generation of new neurons and impair learning or memory. “The elevated CCL11 result was very interesting, because it could potentially explain why some Covid survivors experience cognitive symptoms,” he says.

Interestingly, CCL11 was found elevated in the brains of ME/CFS too, in this study.


Another area these researchers looked at was the effect of COVID on the brain's oligodendrocytes; these are cells which create the myelin insulation on neurons, which facilitates neuron to neuron communication:

[COVID] infected mice had lost approximately one-third of their mature oligodendrocytes, and had a statistically significant drop in myelination compared to mice in a control group.

In terms of therapeutic interventions, if we can find substances which reduce CCL11 secretion, then that may help treat brain fog.

I found this paper which says blackcurrant anthocyanins suppress CCL11 secretion. For those in the UK, perhaps drinking lots of the blackcurrant drink Ribena might be beneficial.

Specifically, the paper found the blackcurrant anthocyanins delphinidins and cyanidins were involved in CCL11 suppression.

There is a supplement called Delphinol which contains delphinidins; and there is a supplement called Biotest Indigo 3G which contains cyanidins.

 

[hapl808]

Thanks for the summary. Would black currant oil be more or less effective than foods containing black currant?

 

[Hip]

Thanks for the summary. Would black currant oil be more or less effective than foods containing black currant?

I think the anthocyanins are in the blackcurrant fruit. In the UK, you can buy fresh blackcurrants from the supermarket; but I read something about blackcurrants being banned in the US.

 

[hapl808]

That's interesting. I had no idea - just looked up and apparently the ban was lifted quite recently so black currant imports are legal in the USA again.

Here's a study that seems to show anthocyanin content remains in commercial jams.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912725/

 

[ljimbo423]

There’s a unique subpopulation of microglia in the white matter called axon tract microglia,” Monje says. These have a specific genetic signature, she continues, and “are exquisitely sensitive to a wide range of insults,” like inflammatory or toxic stimuli.

In response to these stimuli, microglia can become perpetually reactive.

What I highlighted in bold print, sounds just like what ME/CFS researcher Jarred Younger is saying what he thinks the cause of ME/CFS is.

That it's "primed" microglia, causing brain inflammation, making the brain highly sensitive to many different stimulus, that otherwise, would be harmless and not cause symptoms. "Primed" microglia are very sensitive and "reactive".

I can't think of a better explanation for the wide variety and the different degrees of severity of symptoms, both in Long Covid and in ME/CFS, than the brain.

These sensitized or "reactive" microglia, causing brain inflammation and symptoms, could also explain the wide variety of "triggers" for ME/CFS. Like mold, stress, lyme disease, viral infections, and others. All of these things can cause sensitized or "reactive" microglia, according to research.

 

[hapl808]

I can't think of a better explanation for the wide variety and the different degrees of severity of symptoms, both in Long Covid and in ME/CFS, than the brain.

This has always made some intuitive sense to me. The cognitive symptoms, PEM caused by both physical and mental stimulation that would normally be healthy, extreme environmental reactions that don't always correlate to immunological testing, positive reaction to things like Valium, etc.

 

[ljimbo423]

extreme environmental reactions that don't always correlate to immunological testing,

I get extreme reactions to very low doses of almost any supplement. Even ginger root, which is extremely mild, a dose of 100 mg sends my energy soaring and my anxiety with it. I could give dozens of examples like this, to herbs and supplements.

 

[Hip]

What I highlighted in bold print, sounds just like what ME/CFS researcher Jarred Younger is saying what he thinks the cause of ME/CFS is.

That it's "primed" microglia, causing brain inflammation, making the brain highly sensitive to many different stimulus, that otherwise, would be harmless and not cause symptoms. "Primed" microglia are very sensitive and "reactive".

The microglial priming / immune priming theory of ME/CFS, proposed independently by Prof Hugh Perry and Dr Jarred Younger, is an interesting and plausible theory; it involves dual signals activating the microglia, typically an LPS signal plus an interferon gamma signal.

However, this present research on brain fog does not seem involve immune priming; that does not appear to be the mechanism of microglial extra sensitivity (nothing is said about priming in the study).

Rather the published study talks about the "exquisitely sensitive" microglia that inhabit the white matter of the brain. So this subset of white matter microglia appears to be naturally highly sensitive to triggering into an inflammatory state.


This research originated with work on brain fog caused by chemotherapy. It appears that these same super-sensitive white matter microglia are also activated by chemotherapy drugs like methotrexate.

 

[ljimbo423]

However, this present research on brain fog does not seem involve immune priming; that does not appear to be the mechanism of microglial extra sensitivity (nothing is said about priming in the study).

Rather the published study talks about the "exquisitely sensitive" microglia that inhabit the white matter of the brain. So this subset of white matter microglia appears to be naturally highly sensitive to triggering into an inflammatory state.

I just read some of the study. It sounds like it's immune system activation from Covid 19 is what causes the "Reactive microglia". What is causing the "Reactive microglia" in that study, if not immune system stimulation from Covid 19?

I'm not trying to give you a hard time Hip, just trying to understand this a little better.

 

[Hip]

I just read some of the study. It sounds like it's immune system activation from Covid 19 is what causes the "Reactive microglia". What is causing the "Reactive microglia" in that study, if not immune system stimulation from Covid 19?

You could be right; this is the first time I have come across white matter microglia, and do not know anything about them.

The article says:

“There’s a unique subpopulation of microglia in the white matter called axon tract microglia,” Monje says. These have a specific genetic signature, she continues, and “are exquisitely sensitive to a wide range of insults,” like inflammatory or toxic stimuli.

So that suggests to me that these white matter microglia (also called axon tract-associated microglia) are naturally very sensitive to stimuli.

And I searched for the words "prime" and "priming" in the paper, and there was not mention of them.

However, this quote from the study does perhaps suggest that COVID may have increased their reactivity:

Examining the mouse hippocampus following mild respiratory SARS-CoV-2 infection, we found robustly increased microglial reactivity in hippocampal white matter at 7-days post-infection (Figure 4A–B) that persists until at least 7-weeks post-infection

 

[Rufous McKinney]

That's interesting. I had no idea - just looked up and apparently the ban was lifted quite recently so black currant imports are legal in the USA again.

How fascinating! I had no idea.....

currents (in the genus RIBES)...were banned from cultivation in the United States around 1900 and that lasted for over a century. The fruit itself I don't think was ever banned. Currents are related to gooseberries.

Ribes is the alternate host of the invasive White Pine Blister Rust. Which came to North America and damaged our Pines and other woody species.

 

[Rufous McKinney]

The fruit itself I don't think was ever banned.

the fruit seems banned if imported from Northern Europe but maybe Ok if imported from Chile or New Zealand..

The fruits dried could contain the fungus..hence not wanting to import dried fruit, either.

 

[ljimbo423]

Thanks @Hip, that was my basic understanding too, but I didn't read much of the paper, so I wasn't sure if I understood it right.

 

[Hip]

A New Zealand blackcurrant supplement called CurraNZ which has 35% anthocyanins appears to be cheaply available on the UK Amazon.

This supplement appears to be similar to the New Zealand blackcurrant supplement used in the mouse study, which led to a 48% reduction in CCL11.

So this supplement might be worth experimenting with, to see if it improve brain fog.



In the study, gave mice orally 10 mg/kg of a blackcurrant anthocyanin product called Currantex 30, which contains 30% total anthocyanins (this supplement is no longer available, but a similar product called CurraNZ, which is slightly stronger at 35% anthocyanins, is available to buy).

This mouse 10 mg/kg of Currantex 30 works out to a human dose of 0.81 mg/kg, which for a 75 kg person is an oral dose of around 60 mg. One CurraNZ capsule contains 300 mg, so one capsule would be 5 times the equivalent human dose in the study.

 

[Hip]

Another substance which has been shown to reduce CCL11 in vivo is tomatidine, which comes from then stems and leaves of tomato plants, as well as from unripened green tomatoes (at 500 mg per kg). Ref: 1

Tomatidine appears to be available as a supplement, though it's expensive.

 

[Judee]

It seems that in brain fog, specialized microglia in the white matter may have become permanently switched on:

@Wishful???

 

[Wishful]

Well, it does fit into my beliefs about ME, but I can't add anything that would specifically confirm it. It doesn't make me want to rush out to buy blackcurrants or chew on tomato plants. I'll wait for either proper research testing, or some other members who are willing to eat some tomato plants.

BTW, potatoes and tomatoes make my ME symptoms worse, so I'm definitely not willing to experiment with chewing on tomato plants.

 

[Rufous McKinney]

BTW, potatoes and tomatoes make my ME symptoms worse, so I'm definitely not willing to experiment with chewing on tomato plants.

three going green potatoes look dangerous to me right now....I think the currents sound more feasible and better than eating green tomatoes products.

 

[godlovesatrier]

This sounds genuinely realistic and indicative. Thank the lord. They are making progress.

I don't really understand how I'm able to have transient brain fog. I also get brain fog if I take various drugs or supplements. Not always a herx sometimes I just get it from b vitamins I've tried almost all and they all cloud me right up. I feel like I'm floating in a cloud sometimes from these reactions. Other times it will come on after a virus has broken.

But yes not sure how I keep it under control. I'm not convinced it's anything I'm doing. I just think I'm lucky.

This sounds like they might have some treatments one day soon. Makes the illness start to feel a little less shit. If some of us could use our brains (I guess like I can most of the time) part time work wouldn't be out of the question. For those that can remain physically ok for a day or two a week.

Well fingers crossed they continue to find things.