This Is MS Multiple Sclerosis Knowledge & Support Community

No, it's not a cheap science fiction film: it's the revival of a long forgotten suggestion that these cells may have an important role to play in MS, as agents of both damage and repair:

Astrocytes-Friends or foes in multiple sclerosis?

Williams A, Piaton G, Lubetzki C.

Inserm, U711, Université Pierre and Marie Curie, Faculté de médecine, IFR 70, Paris F‐75013, France.

In multiple sclerosis (MS), the presence of demyelinating plaques has concentrated researchers' minds on the role of the oligodendrocyte in its pathophysiology. Recently, with the rediscovery of early and widespread loss of axons in the disease, new emphasis has been put on the role of axons and axon-oligodendrocyte interactions in MS. Despite the fact that, in 1904, Müller claimed that MS was a disease of astrocytes, more recently, astrocytes have taken a back seat, except as the cells that form the final glial scar after all hope of demyelination is over. However, perhaps it is time for the return of the astrocyte to popularity in the pathogenesis of MS, with recent reports on the dual role of astrocytes in aiding degeneration and demyelination, by promoting inflammation, damage of oligodendrocytes and axons, and glial scarring, but also in creating a permissive environment for remyelination by their action on oligodendrocyte precursor migration, oligodendrocyte proliferation, and differentiation. We review these findings to try to provide a cogent view of astrocytes in the pathology of MS. (c) 2007 Wiley-Liss, Inc.

PMID: 17626262 [PubMed - as supplied by publisher]

Dom

I've been waiting for those astrocytes to return. Patiently.

Seriously, I've never been able to quite figure out if "reactive gliosis" and the glial scarring in MS were related to the astrocytes, but that abstract seems to suggest they are.

Here's a recent abstract on testosterone.

Testosterone decreases reactive astroglia and reactive microglia after brain injury in male rats: role of its metabolites, oestradiol and dihydrotestosterone

Previous studies have shown that the neuroprotective hormone, testosterone, administered immediately after neural injury, reduces reactive astrogliosis.

In conclusion, testosterone controls reactive gliosis and its metabolites, oestradiol and dihydrotestosterone, may be involved in this hormonal effect. The regulation of gliosis may be part of the neuroprotective mechanism of testosterone.

Do you think this research suggests testosterone (estradiol too) might reduce glial scarring? I assume that would be a "friend" and not a "foe" for people with MS. Is that the right assumption? Or, is it totally unrelated? Your comments would be most welcome.

Thanks!

Sharon

Hi Sharon,
Yes, I'm pretty certain that astrocytes are responsible for forming the glial scar. When you look as all the brain processes they are involved in, the whole concept of MS being a " disease of astrocytes" becomes very plausible: for example, they release and mop up neurotransmitters such as glutamate, ATP and GABA; they provide nutrients to neurons; their extensions can attach to endothelial cells and thus form part of the blood brain barrier; they help to control blood flow within the brain, and they release a protein which stimulates oligodendrocytes into action.

The research you quoted certainly suggests to me that you are right to assume that those hormones may reduce, delay, or ameliorate glial scarring. This is probably a good thing, since the scar tissue prevents further repair and regrowth. It may be that this tissue forms so that the body doesn't waste precious resources in a long repair job on cells which, in the normal run of things, have plenty of backup. With our modern lifestyle, we could afford to expend that extra time and energy, so perhaps delaying scar formation, (along with providing the correct signalling molecules), might be very important.
However, if the scar tissue is there for a reason I haven't thought of, it's possible there might be some negative consequences in preventing it.

Dom

Thanks for all that info, explanation and perspective.

There might be a full line up of “hormones” that could potentially impact glial scarring. Two more are DHEA and progesterone. Here’s some info on DHEA in spinal cord injury.

DHEA significantly increased the area of white matter spared at the epicenter and reduced the area of reactive gliosis surrounding the lesion

And info from TBI research on progesterone

These results provide evidence of the anti-apoptotic and anti-astrogliotic effects of progesterone

Thanks again Dom--your knowledge and wisdom are tremendous and greatly appreciated.

Sharon

btw--So is your humour.

TwistedHelix wrote:However, if the scar tissue is there for a reason I haven't thought of, it's possible there might be some negative consequences in preventing it.

Purely a stab in the dark, but could the scar tissue be formed to stop the neuron dying by being unprotected? I have herd that myelin may not only serve to increase the electrical speeds, but may also provide nourishment to the nerve. Maybe scarring does this to some extent, better than nothing?

Hi Sharon,
I hope there are researchers out there who know as much about hormones as you do: it looks to me as if they play a key role in this disease. Would you agree that the really crucial thing is not the absolute levels of each hormone, but the balance and ratio of them all in relation to each other?
Glad you appreciate my sense of humour – I've tried to keep it in check, but it keeps leaking out all over the place!
One thing I forgot to mention earlier: as far as I understand it, " reactive gliosis" originally used to mean the brain's own response to trauma, which didn't involve things from outside the CNS like white blood cells. Over time that definition has expanded to include external agents and swelling, etc., and morphed into the term " neuroinflammation".

Hi Cure,
If they refuse to listen about hormones, then I hope more researchers will take a few " stabs in dark" like this!
I don't think scar tissue supports axons in this way – I've always imagined it to be like the last ditch attempt of a shoddy builder: kind of, " I can't fix the wiring: better just plaster over it and use a different lamp".
In fact, it actively discourages neural growth by releasing growth inhibitors, trouble is, I'm starting to disbelieve everything which used to be "accepted fact" – in my inbox only this morning was some information about glial scar tissue: there is a molecule called CHL 1 which is known to promote neurite growth, neuronal migration, and survival in Vitro. Fact. Trouble is, in scar tissue it becomes an inhibitor:

...indicate that CHL1 is a glial scar component that restricts posttraumatic axonal growth and remodeling of spinal circuits by homophilic binding mechanisms

So, just because something is thought not to be the case at the moment, it doesn't mean that next week some new evidence won't turn up proving the exact opposite

TwistedHelix wrote: "I'm starting to disbelieve everything which used to be "accepted fact" –
So, just because something is thought not to be the case at the moment, it doesn't mean that next week some new evidence won't turn up proving the exact opposite

Hi Dom,
Honestly, not to badmouth the researchers, but diregarding all MS "truisms", even recent ones, is the best attitude to take.

Get your hands on some kind of "History of MS" book. The one I read was available free on the State of Michigan E Library after typing in my driver's license number...there must be something similar in England.

With a little time to invest and an open but questioning mind you'll quickly see that what you mentioned above is absolutely true. There have been generation after generation of MS "truisms" which have changed from time to time but have been no less and no more accurate than the ones they replaced.

Why should we believe that this generation of "truisms" and researchers are any more accurate than the ones which preceeded them?

That might make the situation seem terribly hopeless but to the contrary I think things are more hopeful now than they've ever been.

Bob

Dom

You wrote:

I hope there are researchers out there who know as much about hormones as you do: it looks to me as if they play a key role in this disease.

I sincerely hope there are researchers out there who know a lot more about hormones than I do. I'm just not sure there a lot of them in MS research. Honestly, I feel as though I know very little, but I have done some reading and I definitely agree with you that it's entirely possible hormones play a key role (or roles) in this disease.

Would you agree that the really crucial thing is not the absolute levels of each hormone, but the balance and ratio of them all in relation to each other

Based upon what I've read I'd definitely agree that it's the balance and ratio of them all in relation to one another that's crucial and more important than the absolute levels. I think this recent abstract (unfortunately not MS research) supports that concept.Sex differences in brain damage and recovery of function: experimental and clinical findings

recent data showing that fluctuations in hormonal status during the menstrual and estrous cycle can play a determining role in functional outcome in both normal and brain-injured females,

Of course women with MS have been reporting fluctuations in MS symptoms on a regular basis for how many decades? (I just had to be sarcastic)

The only qualifier with respect to the "absolute level" would be that it seems like each one should be within the "normal" range--not excessively high or low. It's my understanding that hormones may exert opposite effects at extremely high and/or low levels and there is a whole lot that is unknown.

I think that with one or two exceptions I've been amazed that the "neuroprotective" properties demonstrated in mice have been with physiological levels of the hormone, that is the normal level that one would expect to have.

Now, in the TBI and progesterone trial large doses of progesterone were used. And, even though it's a little OT, I want to squeeze in the definitive quote from this abstract: Does Progesterone Have Neuroprotective Properties?

We now know that it is produced in the brain, for the brain, by neurons and glial cells in the central and peripheral nervous system of both male and female individuals.

And Dom and Bob--agreed, there may be new evidence next week proving the exact opposite. Unfortunately, there are probably fewer people doing research on hormones and the brain than there are doing research in MS, so it may take longer for the opposite evidence about hormones to emerge.

Take care and thanks Dom for the additional info about "reactive gliosis", AKA, "neuroinflammation". Too much.....

Sharon