How environmental factors may impact vagus nerve/brainstem/neuroinflammation in ME/CFS and LongCovid

Shanti1

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Dr. Michael VanElzakker and Dr. Amy Proal discuss vagus nerve to dorsal brainstem signaling and microglial activation (neuroinflammation). They further examine how environmental factors may impact this signaling in patients with ME/CFS and LongCovid.

 

ljimbo423

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Great video!

IMO, they have the primary causes of ME/CFS and the right basic pathology.

Multiple infections, (and I think other things), that cause sensitized microglia and neuro-inflammation. Which they think is the primary cause of symptoms, as does Jarred Younger.

I'm really happy to see them integrating dysbiosis, and leaky gut, more and more into their hypothesis, as a cause of ME/CFS.

And how inflammation from dysbiosis can activate the vagus nerve around the gut, travel up the vagus nerve to the brain stem, activate microglia, which activates the sickness response.

Which can cause fatigue, pain, malaise, and many flu-like feelings, and I think Micheal even said it can cause anxiety. I really feel that they have the best hypothesis I've heard to date.

Once the microglia become sensitized, it doesn't take very much to fully reactivate them. This is what causes PEM, I think. I almost always feel sick to some extent, with fatigue, malaise, pain, etc.

I think this comes from how activated the microglia in my brain are. The less they are activated, the milder my symptoms. The more they are activated, the worse my symptoms are.

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Oliver3

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Sounds very plausible indeed. When I've first taken big anti inflammatory properties, my anxiety and malaise sometimes stop in their tracks.
But then somehow, the body overrides and returns to base suffering.
I've always thought it would be interesting, as s side note to look at the mechanisms behind habituation and see if we can switch them off.
Thymoquinine was brilliant ( inside black seed oil) for me. Lasted months. Wasn't cured but the difference was amazing. Then I habituated..why?
 

ljimbo423

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Thymoquinine was brilliant ( inside black seed oil) for me. Lasted months. Wasn't cured but the difference was amazing. Then I habituated..why?
I wish I knew.

I get a big increase in energy whenever I go up or down on most any supplement. Then after a few days, my energy returns to normal.

My sense is it has something to do with my brain, possibly somehow interfering with the activated microglia, reducing my symptoms and increasing my energy.

One reason I think microglia or neuro-inflammation is involved, is because with the increase in energy comes an equal amount of anxiety.

Also that I think my symptoms are coming from activated microglia. So when my symptoms improve, I think it makes sense that my microglia are somehow being affected by something. Something, is somehow reducing microglia activation in my brain.
 

Oliver3

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I wish I knew.

I get a big increase in energy whenever I go up or down on most any supplement. Then after a few days, my energy returns to normal.

My sense is it has something to do with my brain, possibly somehow interfering with the activated microglia, reducing my symptoms and increasing my energy.

One reason I think microglia or neuro-inflammation is involved, is because with the increase in energy comes an equal amount of anxiety.

Also that I think my symptoms are coming from activated microglia. So when my symptoms improve, I think it makes sense that my microglia are somehow being affected by something. Something, is somehow reducing microglia activation in my brain.
I agree with you. When I took the black seed oil, my energy improved, my anxiety went, my pots subsided as did my orthastic intolerance.
My friend who has eds( it looks identical to me to CFS) has tried abilify and now won't be without it.
I'm not sure it works on microglia, as well as dopamine but smthg in the brain causing a lot of problems that antihistemic and dopamine enhancers help.
Just off the top of my head is there any suppression of microglia with increases in b vitamins
 

ljimbo423

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Just off the top of my head is there any suppression of microglia with increases in b vitamins
I'm not sure. Taking vitamin B-1 (Thiamine) at about 100 mg a day has stopped 95% of my moderate to severe insomnia. I think I read that benfotiamine can reduce microglial activation, but I'm not sure if regular B-1 does.
 
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Wishful

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What caught my attention in one of their papers is how neuroinflammation can cause latent infections to flare up. Perhaps the studies showing viral infections in PWME are a result of ME messing up our immune systems, making new infections more likely or existing latent infections to show signs. It's that cause/effect question.
 

Nuno

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For proposed treatments I am guessing two fronts?

One for calming the microglia, and other to clear the root cause. Which Microglial inhibitors do we have besides Ibudolast?
 

Learner1

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@Shanti1 Thank you for posting. This is the most important video I've ever seen on ME/CFS, one we should be asking out doctors about - that is, testing and treating the problems mentioned.
For proposed treatments I am guessing two fronts?

One for calming the microglia, and other to clear the root cause. Which Microglial inhibitors do we have besides Ibudolast?
"Protective Effect and Mechanism of Boswellic Acid and Myrrha Sesquiterpenes with Different Proportions of Compatibility on Neuroinflammation by LPS-Induced BV2 Cells Combined with Network Pharmacology" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864549/

"Effects of Curcumin on Microglial Cells - PubMed" https://pubmed.ncbi.nlm.nih.gov/30949950/
 

Shanti1

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IMO, they have the primary causes of ME/CFS and the right basic pathology.
Yes, I think this is abig piece. The theory really explains so many symptoms from nausea and anxiety to dysautonomia. The fact that CCI can cause ME/CFS related to brain stem compression is evidence that inflammation in the brain stem area can lead to many hallmark symptoms. In the recent IACFS conference, there were two cases presented where pwME due to CCI were given cervical spine braces, which led to a resolution of symptoms. Also interesting that TBI can lead to ME/CFS symptoms. While I think what is described in the video is a very important pathway to ME/CFS, I think there are other mechanisms that can be involved. For example, have been observing that lack of tissue oxygenation/ability to use oxygen seems to be a common underlying theme in ME/CFS. While sometimes this could be due to dysautonomia from brain stem inflammation, I think there are other mechanisms that can lead to poor oxygenation.

I'm really happy to see them integrating dysbiosis, and leaky gut, more and more into their hypothesis, as a cause of ME/CFS.
Me too, it is a big piece of the puzzle for many people as we are finding that there is almost no aspect of health that the microbiome doesn't influence, but it is particularly active in modulating our immune function. That gut-brain connection through the vegas nerve is so real! Some of the metabolites made by the microflora can also pass through the BBB directly and influence brain function. I am extremely sensitive to foods, especially carbs (I think you posted somewhere else that you are too). If I eat sugar, I go into a comatose-like state.

Thymoquinine was brilliant ( inside black seed oil) for me. Lasted months. Wasn't cured but the difference was amazing. Then I habituated..why?
I get a big increase in energy whenever I go up or down on most any supplement. Then after a few days, my energy returns to normal.
Really common for me too. It's as if the body is sensing that it should be in a shutdown "cell danger" response mode, so if I find out a way to give myself more energy, it finds a way to take it away. When I find something that does work for me, it is usually because I've actually hit on a root cause of my illness (ie valacyclovier and desmopressin have really helped me).

@Shanti1 Thank you for posting. This is the most important video I've ever seen on ME/CFS, one we should be asking out doctors about - that is, testing and treating the problems mentioned.
I thought it was one of their best in terms of consisely presenting the theory and also giving a mention to toxins, dysbiosis and mold as causitive agents.

Identifying and addressing stelth infections can be so important. Its too bad that there aren't better tests for so many of these hidden infections. For those who have active pathogens, the chances of calming down microglia are much better once the pathogen has been addressed. Thanks for posting the great suggestions for neuroinflammation.
 
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Shanti1

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Also thinking some of the TBI protocols out there would be helpful for brain restoration for ME/CFS folks since activated microglia and brain hypoperfusion are common theams in each condition.
 
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Also thinking some of the TBI protocols out there would be helpful for brain restoration for ME/CFS folks since activated microglia and brain hypopurfusion afe common theams in each condition.
I just ordered some cerebrolysin - I think a few people here have used it with success (not sure exactly). Your post made me think of it though as it has been used quite successfully to treat TBI in a few studies.
 

Shanti1

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I just ordered some cerebrolysin - I think a few people here have used it with success (not sure exactly). Your post made me think of it though as it has been used quite successfully to treat TBI in a few studies.
I think peptide therapy is interesting and promising, especially when it comes to restoring function. I tried cerebrolysin a few years ago before my ME/CFS diagnosis when I was really struggling cognitively. It didn't help me at that time, but it might now since I have cleared some of my underlying issues.
 

Learner1

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I thought it was one of their best in terms of consisely presenting the theory and also giving a mention to toxins, dysbiosis and mold as causitive agents.
Me too, it is one that every ME/CFS patient, their family/caregivers and doctors should read.
Identifying and addressing stelth infections can be so important. Its too bad that there aren't better tests for so many of these hidden infections. For those who have active pathogens, the chances of calming down microglia are much better once the pathogen has been addressed. Thanks for posting the great suggestions for neuroinflammation.
You're welcome. I agree about the stealth infections. I know so many patients who finally found that they did indeed have some sort of infection, particularly herpes family or enteroviruses going on.
 

Nuno

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Me too, it is one that every ME/CFS patient, their family/caregivers and doctors should read.
You're welcome. I agree about the stealth infections. I know so many patients who finally found that they did indeed have some sort of infection, particularly herpes family or enteroviruses going on.
I absolutely agree about the infections, the hard part, which I think will be the answer, is knowing

1-why the system is not clearing them?

2-How to really know which pathogen is causing the problem? Since healthy people also have them, this is the hardest question.

3-How to diferenciate between pathogen virus or friendly virus for example? We are now seeing sarscov2 virus particles in the gut of healthy humans, and this absolutely blows my mind.