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

tango

Senior Member
Messages
165
Location
New Zealand
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

Senior Member
Messages
165
Location
New Zealand
Donna Jackson Nakazawa also mentions Ketamine in the book as a possible remedy but I am not brave enough to try that!
 

Wishful

Senior Member
Messages
5,811
Location
Alberta
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.
 

pattismith

Senior Member
Messages
3,966
@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

Senior Member
Messages
3,966
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
 
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Wishful

Senior Member
Messages
5,811
Location
Alberta
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

Senior Member
Messages
2,178
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

Senior Member
Messages
5,811
Location
Alberta
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. :xeyes:
 

Wishful

Senior Member
Messages
5,811
Location
Alberta
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

Senior Member
Messages
3,966
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
 
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