Atrophy

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Atrophy

Postby bromley » Wed Jan 31, 2007 1:50 pm

Interesting answer about atrophy and axonal damage. Good to hear that research is very active in this area and work underway looking at neuro-protection. Sometimes when I read these sorts of answers, I'm still not clear if it is the myelin which is damaged first and then the axons, or the axons are damaged first resulting in secondary damage to the myelin!

http://www.msanswers.ca/QuestionView.aspx?L=2&QID=249

Ian
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Postby Chris55 » Wed Jan 31, 2007 4:28 pm

It is my understanding that it is the continuous damage to the myelin that ultimately destroys the axon. The myelin does regenerate, albeit weakly, for quite some time and than loses its ability and the axons become destroyed permanently. (God, what a lovely thought!)
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Postby Lyon » Wed Jan 31, 2007 5:21 pm

Thanks Ian,
I should bookmark that site because it seems that guy quite consistantly answers interesting questions (or so it seems from your pointing it out).

Wouldn't it almost HAVE to be a situation in which the myelin goes first and then the axon? I've never seen any reason to think that it could happen the other way around.
Bob
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Axonal Loss Without Demyelination

Postby Shayk » Wed Jan 31, 2007 6:09 pm

Bob
I've never seen any reason to think that it could happen the other way around

But it apparently does...

Axonal loss in normal-appearing white matter in a patient with acute MS
22% axonal loss at segment C7, but grossly normal immunostaining for myelin

Confocal and electron microscopy revealed myelin sheaths without axonal content

CONCLUSIONS: These studies confirm axonal degeneration in the absence of myelin loss as one histopathologic correlate to abnormal MR findings in patients with MS

Sharon
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Postby Lyon » Wed Jan 31, 2007 6:19 pm

Hi Shayk,
I was going to ask you where you got those quotes but then I noticed that the text is a link. One of these days you're going to have to tell me how to do that!

I'll read it. Thanks!
Bob

Wow, I read it and it doesn't beat around the bush. In that case it seemed pretty conclusive. I'm going to have to think on this one because that's a big variation from what seems to be commonly accepted. I notice that is from 2001. I need to find out what other researchers make of it. Didn't seem in the time since to change what other researchers think?
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Making link with text

Postby lyndacarol » Wed Jan 31, 2007 7:11 pm

Lyon, I'll be watching for Shayk's reply, too. Like you, I have wondered for a while how some folks (not only Shayk, but dignan and Napay, among others, I think) make a link with text.

This could probably be answered by Arron, too; but I have already asked him too many dumb questions, I'm embarrassed to ask him one more.
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Postby Lyon » Wed Jan 31, 2007 7:16 pm

Hi Lynda,
Exactly, NAPAY does it too and I was going to ask her how earlier but I hadn't thought to ask until now.
Bob
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Re: URL encoding

Postby NHE » Wed Jan 31, 2007 9:25 pm

Lyon wrote:I was going to ask you where you got those quotes but then I noticed that the text is a link. One of these days you're going to have to tell me how to do that!

Here's an example...
Code: Select all
[url=http://www.thisisms.com/forums.html][color=blue]ThisIsMS[/color][/url]

More BBCode formatting tips can be found here.
http://www.thisisms.com/forum-faq-bbcode.html

Note that using the above code for URLs keeps very long URLs from causing the browser page to stretch to a new width to accomodate the long URL. This can make reading a thread both annoying and difficult as it requires scrolling the window back and forth to read each line.

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Re: URL encoding

Postby Lyon » Thu Feb 01, 2007 6:32 am

Thanks NHE and thanks for the link to the bbcode info. I never could have looked that up because I don't know what bbcode is and wouldn't have associated it with this situation.
NHE wrote: Note that using the above code for URLs keeps very long URLs from causing the browser page to stretch to a new width to accomodate the long URL. This can make reading a thread both annoying and difficult as it requires scrolling the window back and forth to read each line. NHE
I think you mentioned this and "tinyurl" a long time ago and I didn't understand this part so I downloaded tinyurl. I like this option better!
Bob
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Neuren Pharmaceuticals

Postby gwa » Thu Feb 01, 2007 9:13 am

bromley,

I have been watching this Australian company for several years. It is developing treatments for neuro degeneration and brain trauma repair.

The US FDA recently directed the company to enter stage 3 trials with their first drug, Glypromate, and put it on a fast track orphan drug status. Neuren is working on this med with the US Army Walter Reed Hospital brain trauma researchers.

This trial will further test brain repair for stroke victims and brain trauma patients and will end in 18 months.

Their next drug in their pipeline is NNZ 2566. This is an oral drug that penetrates the BBB and it will be used for axonal repair for brain trauma as well as multiple sclerosis. It is now in phase 2, or soon will be, and should be on the market in 4 to 5 years.

There is quite a lot of information on their site.

http://www.neurenpharma.com/

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Postby bromley » Thu Feb 01, 2007 9:39 am

GWA,

Thanks - I've also been keeping tabs on this company. I think there is quite a bit of read across from the various CNS diseases where there is inflammation / neuro-degeneration. So a break-through in one disease should be beneficial to others. I recenlty saw that there is a small stem cell trial for people with Batten's disesase which will start at the end of the year. This is a grim degenerative disease, but hopefully it will show some success and pave the way for other human trials for other diseases of the CNS.

Ian
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axons

Postby gwa » Thu Feb 01, 2007 10:13 am

Anything that will protect/repair axons will benefit a lot of diseases.

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Axonal Loss and Demyelination

Postby Shayk » Thu Feb 01, 2007 6:55 pm

NHE—Thanks so much for answering the question.

Bob
Didn't seem in the time since to change what other researchers think?

Generally speaking I think it most definitely has but not nearly enough IMO.

Here’s some 2006 research:

The contribution of demyelination to axonal loss in multiple sclerosis

The traditional notion that multiple sclerosis is a primary demyelinating disease has led to a plaque-centred view of both aetiology and the pathogenesis of disease progression. The presence of axonal loss has received increasing recognition. However, the relative roles of demyelination and axonal loss have not been fully clarified in multiple sclerosis nor have their possible interrelationships been elucidated.

Unexpectedly, after adjusting for sex, age and duration of disease, correlations between total plaque load and axonal loss in both the corticospinal tract and sensory tracts were weak or absent at each level investigated. Since there was little correlation between plaque load and axonal loss, the possibility that demyelination is not the primary determinant of spinal cord axonal loss warrants consideration.


Some 2005 research:

MRI Evidence for MS as a Diffuse Disease of the CNS
All of this calls for the concept of MS as a focal, inflammatory demyelinating, WM disease to be reexamined and to start viewing MS as a diffuse CNS disease with an important neurodegenerative component. This is central for identifying novel and effective treatment strategies

Ian

Just for you…..more on the potential of hormones. :) This is Alzheimer’s research and “allopregnanolone” is a metabolite of progesterone.

Therapeutic potential of neurogenesis for prevention and recovery from Alzheimer's disease: allopregnanolone as a proof of concept neurogenic agent
Our efforts have been directed towards discovery and development of small, blood brain barrier penetrant molecules to promote endogenous proliferation of neural stem cells within the brain. These endeavors have led to the discovery that the neurosteroid alloprognanolone (APalpha) is a potent and highly efficacious proliferative agent in vitro and in vivo of both rodent and human neural stem cells. Results of our in vitro studies coupled with our more recent analyses in the triple transgenic mouse model of AD suggest that APalpha is a promising strategy for promoting neurogenesis in the aged brain and potentially for restoration of neuronal populations in brains recovering from neurodegenerative disease or injury
.

Take care all

Sharon
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Axonal Loss first and Demyelination second

Postby Lyon » Thu Feb 01, 2007 7:57 pm

Hi Sharon,
Shayk wrote:Generally speaking I think it most definitely has but not nearly enough IMO.
I haven't had a chance to read any more so I'm still as in the dark as I was last night.

I have to admit that I wouldn't know a Th1 from a Th2 response and 90% of the technical jargon I read is over my head.

What I do well is visualize and obsess. I take the abundance of possibilities (avoiding the things I don't have a chance of understanding) and run them through my head again and again a million times until things come together and make some kind of sense. Of course none of that results in provable fact...maybe untested and never to be tested theory would be the best description. I imagine that's what a lot of us do here.

Although it has nothing to do with what is or what isn't I'd really like to think that the myelin goes first and then the axon because with that being the case I can make sense of the relapsing/remitting aspect. I absolutely can't find any way to justify relapsing/remitting if the axon goes first.

I'll read up on it this weekend and give you my critique :lol:

I may have gotten the wrong idea but you seem to be pretty optomistic about this. If so, I don't need links, just make a convincing argument please.

Bob
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