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

[leela]

What a great thread @Hip. Thank you so much.

 

[Hip]

@OverTheHills
NAC raises intracellular glutathione levels, as does undenatured whey protein, so if this is one of the reasons NAC benefits, then taking 2 or 3 heaped teaspoons of undenatured whey daily may also provide benefits. There are several threads on this forum on NAC.

 

[carmadw]

Hallo, please help me, how much of a dose would i it need for dmx to inhibit microglial activation?
Different sources use different dosages, from very high up to 439mg for neuropatic pain) to very low)( the study that is given here as a source, but the dosage there is for mices and its quite difficult to me to figure out which dose a human being may need)

Its really important...
Another question.... Doesnt cortison also inhibit microglial activation?

 

[carmadw]

Oh i forgot to say thanks for your help, but another question came up...
Will ldn block the effect of dmx?

 

[Hip]

Hallo, please help me, how much of a dose would i it need for dmx to inhibit microglial activation?

Dmx?

 

[carmadw]

Dmx?

Dextromethorphan
Some compare it to ldn, so i wonder if youshoul start with a low dose as well if you have cfs

 

[Hip]

I tried dextromethorphan 15 mg twice daily at one time, but it not help my ME/CFS.

According to this study, dextromethorphan potentiates mu-opioid agonists.

Now LDN does several things, but one of them is to antagonize mu-opioid receptors for a few hours, so when LDN is taken at night, so there is a compensatory increase in beta-endorphin the following day, which will agonize the mu-opioid receptors. By also taking dextromethorphan the following day, you might conceivably further potentiate and enhance the effects of this endorphin on the mu-opioid receptors.

 

[carmadw]

Maybe 15mg was to high f a dose, j just dont k ow if there s a similar immunmodulating reacti to expected...

I have got one week to create alist of meds, that will definitly block my microglia cells...

UUnfortunately didnt many user reply t this thread to exchabge experiences...

 

[lansbergen]

In order to reduce these ME/CFS symptoms of fatigue and brain fog, inhibiting microglial activation may be a good strategy.

I want my microglia to do their job. I do not want to suppress the guardians against pathogens,

 

[Rrrr]

i have yet to read this whole thread, so not sure if this study was posted already. reminder, MLV (Murine Leukemia Virus) was somehow (how?) associated with XMRV, back in the day.
____
http://jvi.asm.org/cgi/content/full/83/10/4912
http://jvi.asm.org/cgi/content/full/83/10/4912

Journal of Virology, May 2009, p. 4912-4922, Vol. 83, No. 10
0022-538X/09/$08.00+0 doi:10.1128/JVI.02343-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Neurodegeneration Induced by PVC-211 Murine Leukemia Virus Is Associated with Increased Levels of Vascular Endothelial Growth Factor and Macrophage Inflammatory Protein 1

and Is Inhibited by Blocking Activation of Microglia
Xiujie Li, Charlotte Hanson, Joan L. Cmarik, and Sandra Ruscetti*

Laboratory of Cancer Prevention, National Cancer Institute—Frederick, Frederick, Maryland 21702

Received 10 November 2008/ Accepted 28 February 2009

ABSTRACT
PVC-211 murine leukemia virus (MuLV) is a neuropathogenic retrovirus that has undergone genetic changes from its nonneuropathogenic parent, Friend MuLV, that allow it to efficiently infect rat brain capillary endothelial cells (BCEC). To clarify the mechanism by which PVC-211 MuLV expression in BCEC induces neurological disease, we examined virus-infected rats at various times during neurological disease progression for vascular and inflammatory changes. As early as 2 weeks after virus infection and before any marked appearance of spongiform neurodegeneration, we detected vessel leakage and an increase in size and number of vessels in the areas of the brain that eventually become diseased. Consistent with these findings, the amount of vascular endothelial growth factor (VEGF) increased in the brain as early as 1 to 2 weeks postinfection. Also detected at this early disease stage was an increased level of macrophage inflammatory protein 1α (MIP-1α), a cytokine involved in recruitment of microglia to the brain. This was followed at 3 weeks postinfection by a marked accumulation of activated microglia in the spongiform areas of the brain accompanied by an increase in tissue plasminogen activator, a product of microglia implicated in neurodegeneration. Pathological observations at the end stage of the disease included loss of neurons, decreased myelination, and mild muscle atrophy. Treatment of PVC-211 MuLV-infected rats with clodronate-containing liposomes, which specifically kill microglia, significantly blocked neurodegeneration. Together, these results suggest that PVC-211 MuLV infection of BCEC results in the production of VEGF and MIP-1α, leading to the vascular changes and microglial activation necessary to cause neurodegeneration.

 

[RustyJ]

http://medicalxpress.com/news/2016-01-beneficial-effects-blocking-brain-inflammation.html

They gave the mice oral doses of an inhibitor that blocks CSF1R and found that it could prevent the rise in microglia numbers seen in untreated mice as the disease progressed. In addition, the inhibitor prevented the loss of communication points between the nerve cells in the brain associated with Alzheimer's, and the treated mice demonstrated fewer memory and behavioural problems compared with the untreated mice.

 

[anciendaze]

Just wanted to bump thread with recent news about microglial activation in Alzheimer's.

 

[roller]

Thanks, very interesting.
I haven't really tried anti-virals yet.
But also think Glial cells maybe strongly involved, in whatever the 'disease' really is.

I tried self-heal from olympian labs - what is/was marketed as anti-HIV sort of.
This Prunella Vulgaris is a popular herb, being used since ancient times and helpful against viruses, i understand.
In addition, i read it may 'fix' some unbeneficial HLA (haplotype) issues I may have.

I can't describe how shit i felt.

As an antiviral, it should be good against microglial activiation ?


http://www.ncbi.nlm.nih.gov/pubmed/15702244
Immune modulatory effects of Prunella vulgaris L.
Fang X1, Chang RC, Yuen WH, Zee SY.
Author information

Abstract
Prunella vulgaris L. (Labiatae) is a perennial plant known as 'self-heal' in Western herbal medicine. It has a wide array of biological effects exhibiting numerous therapeutic potentials. Its anti-microbial effects including anti-viral and anti-bacterial effects are, presently, receiving increasing attention. While its anti-viral effects are attributed mainly to the inhibition of virus replication, the biological mechanisms of its anti-bacterial effects or actions remain unknown. In view of the fact that polysaccharides isolated from medicinal herbs often function as biological response modifier of body immunity, we hypothesized that the anti-microbial effect of polysaccharides isolated from P. vulgaris is probably also mediated via immune modulation. We have isolated four polysaccharides containing fractions from P. vulgaris, one of the fractions, PV2, could markedly stimulate the production of superoxide and nitrite representing nitric oxide from murine macrophage RAW264.7 and brain macrophage BV2 cells. The amount of nitrite and superoxide produced after PV2 stimulation was as high as that seen in stimulation using bacterial endotoxin lipopolysaccharide (LPS), and this stimulatory response is dose-dependent. In addition to monocyte/macrophage, PV2 also stimulated the proliferation of splenocytes. In this study, we have shown that the polysaccharides isolated from P. vulgaris have marked immune stimulatory effects, which may bring about the anti-microbial effects of P. vulgaris.

 

[wastwater]

Alzheimer's and CSF1R and the link to breast cancer and leukaemia.
Gcmaf mentions macrophages.
Idea of a spectrum of micro glial activation,beginning with autism through me/cfs MS schizophrenia etc and ending at Alzheimer's
https://en.wikipedia.org/wiki/Colony_stimulating_factor_1_receptor

 

[Little Bluestem]

I so hope they are wrong on that. In the beginning, some people worried that CFS might be related to AIDS. I have always been more concerned that it might be related to Alzheimer's.

 

[roller]

all those diseases might be caused by inflammation.
ongoing inflammation causes glial activation, i understand.
how about finding and treating the inflammation?

 

[lansbergen]

how about finding and treating the inflammation?

How about finding the cause of the inflamation?

 

[roller]

palmitoylethanolamide

ethanol converts to formalin (formaldehyde) in the body?
which would make a very good antibacterial/antiviral/antifungal/?

means, it would reduce glia cells by reducing the unterlying inflammation - perfect.

(but i think they may have tested something else, sorry)

 

[Nelly Lenz]

Hip, Thanks for this list, with the citations as well. Just an fyi, a lot of the things you took are vasodilators, especially the ones that you took in higher doses (skullcap, resihi in particular, hgw, ginseng). I tend to feel worse the day after taking a vasodilator but not notice it the day I take it, so I wonder if that plays into it.

Also fair warning about the list is that the neuroprotective effects of the drugs/herbs are explored in vitro in most studies. Where they are studied in vivo, I have found that very few exert these effects at normal doses taken. For example, the powerful microglia inhibiting effects of minocycline are found at doses of 50mg/kg to 10mg/kg which would be close to a gram a dose in me, even the lowest dose that showed any changes at all, would be 5x the normal daily dose, and the change in microglia outputs was quite small at that dose. I get going for synergy, but I'm not sure it will happen with a lot of these drugs at safe doses.

 

[Hip]

Where they are studied in vivo, I have found that very few exert these effects at normal doses taken. For example, the powerful microglia inhibiting effects of minocycline are found at doses of 50mg/kg to 10mg/kg which would be close to a gram a dose in me

If these are in vivo animal studies, one thing to watch out for is the conversion between animal and human doses. It is not just a case of multiplying the per Kg dose by the human body weight to get the human dose. You also have to divide the dosage by a certain factor, a factor of around 12 for mice. See page 7 of this document.