Jerry Silver and Other Discussion from ChinaSCINet Update

[lunasicc42]

wise, once you stated that you may be accused of just trying to raise funds if you pre-release any positive preliminary results of the trial.... How can that be construed as a bad thing?
Yes do whatever can be done to raise funds...

[ResidentBio]

I'm glad this thread is changing for the better. I'm all for debate but with the right tone and time. I hope wise efforts shows promising results in 2013, and also hoping Dr Silver's route finds its way to human trials. As for the tissue, hopefully in the end there would be an agreement on what is the best way, even a mixed trial testing both theories.

Even if we are 5-10 years away I'm exited by what you guys are doing now. Plz keep sharing. Knowledge has given me strength to keep on going.

[jsilver]

Learn from yesterday, live for today, hope for tomorrow. The important thing is not to stop questioning.
Albert Einstein


I agree, do others?

[lynnifer]

Agreed.

[kivi66]

"Moe, really, just a little respect to the man who right now developes technique that may substantially improve your condition. Trust me, that won't hurt your EGO."

Why that was deleted? Jim, again?

[Jim]

Was me.
I removed the post by Moe to Dr. Silver because it was off topic and unnecessary.

I'm trying to keep things on track.

[Moe]

Was me.
I removed the post by Moe to Dr. Silver because it was off topic and unnecessary.

I'm trying to keep things on track.

Jim, with all respect, All I asked is if he expected an answer on his einstein quote, then I asked him if he could post this to a new topic/tread.

Unless it's ok to go on with other genius quotes here that the obvious smart answers are "I agree" ?

[lynnifer]

Oh obviously.

You've been paralyzed for two minutes? Most of these people have been involved in this for years - decades even.

It's great to see the passion - what about advocacy? Raising funds for the researcher you most believe in?

I learn more in the debates, myself.

[Moe]

Oh obviously.

You've been paralyzed for two minutes? Most of these people have been involved in this for years - decades even.

It's great to see the passion - what about advocacy? Raising funds for the researcher you most believe in?

I learn more in the debates, myself.

Lynnifer, if you're reffering to me, Id be more than interested to what you have to say in detail on these other topics. Feel free to PM me if you like.

[tumbleweeds]

Was me.
I removed the post by Moe to Dr. Silver because it was off topic and unnecessary.

I'm trying to keep things on track.

There hasn't been a post since 1472 that has been on track. This thread is quite clearly titled as being for ChinaSCINet Update. If people want to debate then fine, set up a thread for debates. For those of us looking for UPDATES with what is going on with ChinaSCINet we shouldn't have to slog through six pages of irrelevant posts.

[fourwhlhntr]

There hasn't been a post since 1472 that has been on track. This thread is quite clearly titled as being for ChinaSCINet Update. If people want to debate then fine, set up a thread for debates. For those of us looking for UPDATES with what is going on with ChinaSCINet we shouldn't have to slog through six pages of irrelevant posts.

Jim, thanks for trying to keep thread on track.
Tumbleweeds, wholeheartedly agree that "debate thread" is needed. These children are getting ridiculous!

[NowhereMan]

Really? The FDA says it doesn't. See http://www.fda.gov/forconsumers/byau.../ucm128291.htm .

I think you might be confusing a new erectile dysfunction or ache treatment with a procedure for which there is no alternative treatment.

Well, that is the amount of processing time from when one applies to the FDA to begin human trials. That doesn't include the time of perfecting the pre-clinical work.

This link quotes pre-clinical time as averaging 3.8 years. However, when involving stem cells or gene therapy I would assume that time period is much longer.

http://www.parentprojectmd.org/site/...trials_process

[Wise Young]

In our lab we have been experimenting on strategies to bridge a chronic spinal cord contusive injury cavity. We have found that it is absolutely essential to physically remove the tough scar membrane that surrounds the wound cavity. If we don't remove scar then there is no regeneration and all the stem cells in the world will not by themselves break this down. The scar is present and it needs to be dealt with.

Merry Xmas

Merry Xmas and Happy New Year to you, too.

The contusion model is one of the toughest spinal cord injury models to get axons to regenerate in. However, having looked at many chronically contused spinal cords, I just don't see the "tough scar membrane that surrounds the wound cavity". I know that some studies suggest that a thin basal lamina forms around cavities at the injury site. On the other hand, in a majority of contused spinal cords that we have looked at, we don't see such a "membrane".

Many chronically contused spinal cords have no cavity. Instead, the injury site is filled with a loose matrix of astrocytes with many axons growing into the injury site. The Multicenter Animal Spinal Cord Injury Study (MASCIS) reported this in 1997 [1]. In this study, we examined over 500 contused rat spinal cords. A majority of the contused spinal cords have no cavity. Rather, they have a loose matrix of tissue at the injury site with many axons growing into that matrix.

I do agree with you that tough fibrous "scar" tissues form around cuts of the spinal cord where the dura was not repaired and fibroblasts from outside the spinal cord have invaded into the injury site and astrocytes have proliferated to wall them off. It is interesting that many laboratories have reported regeneration of axons across cut spinal cord injury sites without removing any "scar" tissue from the injury site. The Liu, et al. 2011 paper [2], reporting that PTEN deletion allows massive corticospinal tract regeneration, without anything being done to remove or prevent scar formation, seems to contradict the notion that a physical scar prevents axonal growth.

For a long time, I did not criticize the glial scar theory, agreeing that it can occur and it is one of the barriers to axonal growth especially when a cavity develops at the injury site or a penetrating injury of the spinal cord allows fibroblast invasion into the injury site. However, my attitude towards the theory changed when I first hear Carlos Lima talk in 2003. I remember his talk and my horror at what he described. He described the surgery in which the neurosurgeon removed a piece of spinal cord from the injury site, that they said was "scar", and then they stuffed pieces of nasal mucosa into the cavity.

Then Lima showed the histology of the pieces of removed spinal cord. He showed several slides that had been silverstained. He pointed out how there were many axons in the sections. I don't think that Lima realized what he was saying. When I spoke to him about this after his talk, he claimed that the piece of tissue was "scar". When I asked him how he knew, he said that it felt "tough". I pointed out the axons and asked him what he thought of the axons. He shrugged his shoulders.

This is the danger of the scar theory. In my opinion, it is still an unproven theory but many people, particularly surgeons, are taking it literally and doing crazy things like cutting a chunk of the spinal cord out, saying that it is "scar". Even when they see axons running through the piece of removed tissue, they don't realize that they are cutting axons. They don't consider that "scar" is very likely to form at the transplant site where they are placing autologous nasal mucosa containing many fibroblasts and other cells that do form scar.

There are still surgeons that I talk to around the world who think that it is okay to cut a chunk out of the spinal cord to place a scaffolding in. There are companies, such as In Vivo Therapeutics, who are implying that it is okay to cut out a piece of spinal cord to place their scaffold. There are many biomedical engineering departments with laboratories working on scaffolding to place inside cavities that they have created in the spinal cords. I am not comfortable with this. This is one of the main reasons why I decided to speak out.

Wise.


References Cited

1. Beattie MS, Bresnahan JC, Komon J, Tovar CA, Van Meter M, Anderson DK, Faden AI, Hsu CY, Noble LJ, Salzman S and Young W (1997). Endogenous repair after spinal cord contusion injuries in the rat. Exp Neurol 148: 453-63. Department of Cell Biology, Ohio State University College of Medicine, 333 West 10th Avenue, Columbus, Ohio 43210, USA. Contusion injuries of the rat thoracic spinal cord were made using a standardized device developed for the Multicenter Animal Spinal Cord Injury Study (MASCIS). Lesions of different severity were studied for signs of endogenous repair at times up to 6 weeks following injury. Contusion injuries produced a typical picture of secondary damage resulting in the destruction of the cord center and the chronic sparing of a peripheral rim of fibers which varied in amount depending upon the injury magnitude. It was noted that the cavities often developed a dense cellular matrix that became partially filled with nerve fibers and associated Schwann cells. The amount of fiber and Schwann cell ingrowth was inversely related to the severity of injury and amount of peripheral fiber sparing. The source of the ingrowing fibers was not determined, but many of them clearly originated in the dorsal roots. In addition to signs of regeneration, we noted evidence for the proliferation of cells located in the ependymal zone surrounding the central canal at early times following contusion injuries. These cells may contribute to the development of cellular trabeculae that provide a scaffolding within the lesion cavity that provides the substrates for cellular infiltration and regeneration of axons. Together, these observations suggest that the endogenous reparative response to spinal contusion injury is substantial. Understanding the regulation and restrictions on the repair processes might lead to better ways in which to encourage spontaneous recovery after CNS injury.

2. Liu K, Lu Y, Lee JK, Samara R, Willenberg R, Sears-Kraxberger I, Tedeschi A, Park KK, Jin D, Cai B, Xu B, Connolly L, Steward O, Zheng B and He Z (2010). PTEN deletion enhances the regenerative ability of adult corticospinal neurons. Nat Neurosci 13: 1075-81. F.M. Kirby Neurobiology Center, Children's Hospital, and Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA. Despite the essential role of the corticospinal tract (CST) in controlling voluntary movements, successful regeneration of large numbers of injured CST axons beyond a spinal cord lesion has never been achieved. We found that PTEN/mTOR are critical for controlling the regenerative capacity of mouse corticospinal neurons. After development, the regrowth potential of CST axons was lost and this was accompanied by a downregulation of mTOR activity in corticospinal neurons. Axonal injury further diminished neuronal mTOR activity in these neurons. Forced upregulation of mTOR activity in corticospinal neurons by conditional deletion of Pten, a negative regulator of mTOR, enhanced compensatory sprouting of uninjured CST axons and enabled successful regeneration of a cohort of injured CST axons past a spinal cord lesion. Furthermore, these regenerating CST axons possessed the ability to reform synapses in spinal segments distal to the injury. Thus, modulating neuronal intrinsic PTEN/mTOR activity represents a potential therapeutic strategy for promoting axon regeneration and functional repair after adult spinal cord injury.

[Buck503]

When I spoke to him about this after his talk, he claimed that the piece of tissue was "scar". When I asked him how he knew, he said that it felt "tough". I pointed out the axons and asked him what he thought of the axons. He shrugged his shoulders.

I can't believe there's such a drastic difference of opinion on
this issue.

Is there a difference in the type or amount of trauma that occurs?
The trauma is a lot less severe when a "scar" is surgically removed,
versus a contusion injury. Maybe the injury site can heal better
after controlled, delicate trauma, such as surgical incisions?

[Skipow]

Are there any studies that have been done on surgical interventions when a surgeon removes scar tissue at acute phase vs. not removing scar tissue or damaged areas of the spinal cord and assessing functional recoveries. I'm sure it would be hard to assess as each injury is different, but maybe performed in a lab setting with animals. Also, what have we learned from human cadaver studies and spinal cord injured scar tissue?

Thanks!