Chronic Microglial Activation in ME/CFS, And Its Possible Treatment Using Microglial Inhibitors

[tango]

Donna Jackson Nakazawa: "The Angel and the Assassin" is a good read on microglial activation. She suggests fasting, neurofeedback, transcranial magnetic stimulation, gamma flickering light and fasting as remedies.

 

[tango]

Donna Jackson Nakazawa also mentions Ketamine in the book as a possible remedy but I am not brave enough to try that!

 

[Ema]

Donna Jackson Nakazawa: "The Angel and the Assassin" is a good read on microglial activation. She suggests fasting, neurofeedback, transcranial magnetic stimulation, gamma flickering light and fasting as remedies.

Yes, this was a great read! I did a review of it, https://9gurus.com/how-microglia-brain-cells-contribute-to-chronic-illness/

 

[Wishful]

One thing I wondered about is where microglia come from. I'd read something about them coming from bone marrow, which affected some possible theories about microglia and ME. I just came across this paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627983/ which is about the origin and differentiation of microglia. It seems that microglia are created from cells in the yolk sack, and replacements are grown within the brain. Some monocytes from bone marrow can enter the brain later and work as microglia-like cells, but usually only in special circumstances, such as severe brain damage or major brain inflammation.

I'm not sure what it all means for ME If anything), but I thought it might be useful for anyone thinking about theories involving microglia.

 

[GlassCannonLife]

Anyone have anything interesting to report on this front from recent times?

 

[pattismith]

@Hip Azithromycin also shift Microglia from M1 to M2

Azithromycin protects mice against ischemic stroke injury by promoting macrophage transition towards M2 phenotype - ScienceDirect

Predictive screening of M1 and M2 macrophages reveals the immunomodulatory effectiveness of post spinal cord injury azithromycin treatment | Scientific Reports (nature.com)

Because of this microglia/macrophage shift, Azithromycin has neuroprotective effect, and may also be beneficial for SLE:

Azithromycin promotes alternatively activated macrophage phenotype in systematic lupus erythematosus via PI3K/Akt signaling pathway - PMC (nih.gov)

 

[pattismith]

@Hip

Are you aware ACE inhibitors that cross Blood Brain Barrier have neuroprotective effect:

Captopril, fosinopril, lisinopril, perindopril, ramipril, and trandolapril were classified as BBB-crossing ACE-inhibitors,

Lupus antibodies induce behavioral changes mediated by microglia and blocked by ACE inhibitors | Journal of Experimental Medicine | Rockefeller University Press (rupress.org)

Blood-Brain Barrier Crossing Renin-Angiotensin Drugs and Cognition in the Elderly: A Meta-Analysis | Hypertension (ahajournals.org)

 

[pattismith]

Minocycline still involved in trials to understand its microglia inhibition property: a 2022 mice study

To the end, the study revealed that microglia is critically involved in stress-induced neuroinflammation, which may underlie the molecular mechanism of CUMS-induced anxiety behavior.

Minocycline Ameliorates Chronic Unpredictable Mild Stress-Induced Neuroinflammation and Abnormal mPFC-HIPP Oscillations in Mice | SpringerLink

CONCLUSIONS:

Our results suggest that minocycline modulates LPS-induced microglia and astrocytes activation as well as improves learning and working memory comparable to memantine. Thus, minocycline may have preventive-therapeutic effect in diseases involving neuroinflammation such as AD.

Minocycline Ameliorated LPS-Induced Learning and Memory Impairment by Inhibiting Microglia and Astrocytes Activation in the Hippocampus | IIUM Medical Journal Malaysia

 

[Wishful]

Their results might suggest that minocycline modulates glial activation, but it had no noticeable effect on my ME symptoms, so it's not a sure-fire treatment for ME.

 

[hapl808]

Not sure I'm understand all this @Hip or if I've asked these exactly questions before, but curious about other compounds that seem to affect TLR 4 activation like amitriptyline?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4983275/

Or something like ketotifen? And if there are specific receptors that seem most helpful for microglial activation, CD14, etc. This is an area that seems relevant to me because my headache and brain inflammation feeling is never ending at this point - just 24/7 feeling of heat stroke. But not an area I really understand much about the underlying systems and I have trouble following it.

 

[Wishful]

But not an area I really understand much about the underlying systems and I have trouble following it.

Does anyone really understand it fully? My guess is that even the experts are missing some critical parts of microglial function. Some of the findings from studies on isolated cells may not apply in vivio due to functions or factors they aren't aware of.

As for us having trouble following the science, brainfog really doesn't help.

 

[Murph]

I've never seen this thread before and not read it, but I note that paracetamol deactivates microglia. I find paracetamol extremely useful in reducing brainfog and also as a PEM preventer.

THis study says it does so by reducing the production and release of prostaglandins from microglia

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729401/?report=reader

 

[Wishful]

I find paracetamol extremely useful in reducing brainfog and also as a PEM preventer.

The problem is that it's not a reliable treatment for those symptoms for most people. It does nothing for my ME symptoms. Maybe for you it is working via prostaglanding reduction, or maybe it's some other mechanism specific to your body/ME.

I think a good experiment would be to test all the known glial-modulating chemicals on volunteers, to see if any provide a reliable effect (positive or negative) on a majority of PWME. I'd volunteer.

 

[pattismith]

Targeting brain Renin-Angiotensin System for the prevention and treatment of Alzheimer’s disease: Past, present and future - ScienceDirect

Both candesartan and telmisartan were able to shift BV2 murine microglial cells towards their neuroprotective phenotype (M2) suggesting, therefore, an important role for these two drugs on modulating brain response to inflammatory stimuli (Torika et al., 2018, Torika et al., 2016a).

Moreover, Bhat et al. also reported a reduction in STAT3 activation contributing to decreased gliosis (Bhat et al., 2016).

Indeed shifting microglia to its neuroprotective state is of utmost importance in neuroinflammatory diseases, including AD

NB: the two studies with losartan and Temilsartan in vivo were mice trials with intranasal route