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Thread: Jerry Silver and Other Discussion from ChinaSCINet Update

  1. #61
    I find these discussions to be enlightening.

    This is in essence- the scientific method at work. Thank you both for your time, expertise and educating the community.

    Dr. Silver- I've been trying to read between the lines, but is there a strategy to bring your therapy to trial. What ways can the community help?

    If you were paralyzed what steps would you take to speeding up the process?

    Thank you in advance for your reply.

  2. #62
    I don't know the answer. My injury state is 26 years post with no motor but some sensory. If a procedure meant that some of my cord needed to be cut out, I'd have serious concerns that I could be worse off.

  3. #63
    Quote Originally Posted by Buck503 View Post

    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?
    I was talking about animal studies. In terms of animal models, our laboratory developed and did the most studies of spinal cord contusion. I organized a group called the multicenter animal spinal cord injury study (MASCIS), consisting of eight leading spinal cord injury centers in the United States, funded by NIH. In one study, we studied 500 rats that had been injured with a 10 gram weight dropped 12.5 mm, 25.0 mm, and 50.0 mm onto the thoracic spinal cord.

    The 12.5 mm weight drop produces "incomplete" spinal cord injury from which 90% of rats will recover locomotion. The 25.0 and 50.0 mm weight drops produce severe and complete spinal cord injuries from which 90% and 100% of the rats do not recover weight-supporting locomotion. This is the largest study of contused spinal cords ever done.

    We did not see glial scars surrounding the injury site of the kind that Jerry described. In fact, a majority of the animals do not have a cavity at the contusion site. Instead, they have a loose matrix of glial cells at the contusion site, through which many axons passed. The more severe injuries tended to have more cavities but most of the spinal cords did not have cavities.

    Wise.

  4. #64
    Quote Originally Posted by Skipow View Post
    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!
    With the exception of Carlos Lima's experience, which I describe below, there are no instances that I know of where surgeons have cut a piece of the spinal cord out to remove scar after injury. I did not think that anybody would ever do such an operation for the following reason. First, if there is indeed scar at the injury site to begin with, what will prevent "scar" from forming again after one has cut it out? Second, the there is no evidence that cutting a piece of spinal cord out and putting anything in the hole results in regeneration or functional recovery.

    In 2008, Dr. Zhu Hui and colleagues reported (in a paper that I co-authored) that cutting open the spinal cord from the side at 4-14 days after severe spinal cord injury results in necrotic (dead) tissue oozing out the opening opening. Washing this dead tissue out of the spinal cord resulted remarkable recovery of locomotion in nearly 50% of 30 patients. All the patients had complete ASIA A spinal cord injury before the surgery. All the patients also received intensive locomotor training (6 hours a day, 6 days a week for 3 months). We are planning to do a phase III clinical trial in the coming year, to confirm these results in a multicenter clinical trial.

    Wise.

  5. #65
    Quote Originally Posted by Wise Young View Post
    We did not see glial scars surrounding the injury site of the kind that Jerry described. In fact, a majority of the animals do not have a cavity at the contusion site. Instead, they have a loose matrix of glial cells at the contusion site, through which many axons passed. The more severe injuries tended to have more cavities but most of the spinal cords did not have cavities.

    Wise.
    It's too bad you couldn't observe their research firsthand and
    possibly see what they're seeing. They're still successfully repairing
    animal models, despite carving out sections of cord.

    I don't remember who it was, but I remember a researcher once
    remarked that they could see axons "fishhook" when they hit this
    scar tissue barrier.
    Last edited by Buck503; 12-30-2012 at 08:54 AM. Reason: I felt like it.

  6. #66
    So when it comes to the scar thing, what does everyone think about Hans' research of basically reprogramming the tissue at the site? It sounds kind of sci-fi like, but it may be an idea like this that works. In cases like Wise is talking about where there is no cavity maybe this could be very promising?

  7. #67
    Senior Member Moe's Avatar
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    Quote Originally Posted by havok View Post
    So when it comes to the scar thing, what does everyone think about Hans' research of basically reprogramming the tissue at the site? It sounds kind of sci-fi like, but it may be an idea like this that works. In cases like Wise is talking about where there is no cavity maybe this could be very promising?
    Yes, this could be promising indeed. But I wonder if this 'scar' tissue consists of live cells that can be programmed because if it consists of dead ones that form this "scar" then I don’t see how it can be reprogrammed...?
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  8. #68
    OK, I will attempt one last time to explain the most current understanding of what comprises the "scar" that forms in the spinal cord after traumatic injury. It is surely composed of living cells, their associated extracellular matrices and a variety of other secreted factors. To my knowledge Wise is the only person I know of who denies the existence of this structure, one that has been described classically as well as in the modern literature a multitude of times.

    The scar is formed by reactive astrocytes whose purpose is to physically wall off the inflammatory core of the lesion. Such reactive astrocytes are easy to see with modern immunohistochemical methods. They become extremely hypertrophic over time and they form tightly adherent junctions between each other. Scar forms after penetrating as well as contusion injuries. The scar has an essential function to protect the remaining healthy tissue from the damaging activities of inflammation. Elegant experiments from the Michael Sofroniew lab have beautifully shown that if the scar is removed via a clever molecular/ genetic manipulation, that without scar inflammation becomes uncontrolled and the lesion expands enormously and further damages the spinal cord far beyond that which was caused by the initial injury. Unfortunately scar also blocks nerve regeneration from passing THROUGH the vicinity of they lesion. Over time Schwann cells can invade through the wall of the scar and enter the lesion core. Schwann cells are highly growth promoting and they can attract axons INTO the lesion core. However, such axons become stranded forever inside the lesion. Finally, the pTEN observation is in the mouse which is a species that develops only very narrow scars around a very narrow lesion core. The growth of pTEN stimulated axons is engineered to occur BEFORE scar is able to form. If you listen to Os Stewards presentation from the W2W symposium you will learn that in the rat, pTEN deletion before or after injury is not able to promote regeneration because of the large scar that develops. In complete and utter disagreement with Dr. Young, if you read the current literature, it is clear that scar is something that must be overcome or removed in order to promote true regeneration especially following chronic injury. Furthermore, I believe that his recent claims of regeneration in his human patients are totally unfounded.

  9. #69
    Senior Member lunasicc42's Avatar
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    I have never commented on this for fear of getting it wrong but I came to think that wise doesn't disagree that something is there, he just has an issue about calling it a "scar" by his understanding of the definition of the word "scar"
    But what I Honestly admit, is that, everytime he attempts to explain exactly why he doesn't like to call it a "scar"... He explains a "matrix of gliosis" or something to that effect. I Honestly think: "isnt that just another way of saying 'scar'? "

    I might be confused
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  10. #70

    jsilver

    Quote Originally Posted by jsilver View Post
    OK, I will attempt one last time to explain the most current understanding of what comprises the "scar" that forms in the spinal cord after traumatic injury. It is surely composed of living cells, their associated extracellular matrices and a variety of other secreted factors. To my knowledge Wise is the only person I know of who denies the existence of this structure, one that has been described classically as well as in the modern literature a multitude of times.

    The scar is formed by reactive astrocytes whose purpose is to physically wall off the inflammatory core of the lesion. Such reactive astrocytes are easy to see with modern immunohistochemical methods. They become extremely hypertrophic over time and they form tightly adherent junctions between each other. Scar forms after penetrating as well as contusion injuries. The scar has an essential function to protect the remaining healthy tissue from the damaging activities of inflammation. Elegant experiments from the Michael Sofroniew lab have beautifully shown that if the scar is removed via a clever molecular/ genetic manipulation, that without scar inflammation becomes uncontrolled and the lesion expands enormously and further damages the spinal cord far beyond that which was caused by the initial injury. Unfortunately scar also blocks nerve regeneration from passing THROUGH the vicinity of they lesion. Over time Schwann cells can invade through the wall of the scar and enter the lesion core. Schwann cells are highly growth promoting and they can attract axons INTO the lesion core. However, such axons become stranded forever inside the lesion. Finally, the pTEN observation is in the mouse which is a species that develops only very narrow scars around a very narrow lesion core. The growth of pTEN stimulated axons is engineered to occur BEFORE scar is able to form. If you listen to Os Stewards presentation from the W2W symposium you will learn that in the rat, pTEN deletion before or after injury is not able to promote regeneration because of the large scar that develops. In complete and utter disagreement with Dr. Young, if you read the current literature, it is clear that scar is something that must be overcome or removed in order to promote true regeneration especially following chronic injury. Furthermore, I believe that his recent claims of regeneration in his human patients are totally unfounded.
    Thank you for the work that you are doing for us But can i ask you when do hope to bring you findings to trials I know i dont care a bout scar tissue all we want to know will it work As for that matter any thing will do me as long as it comes quick sorry if this was asked be four or can any one else shed any more light on this
    Last edited by skeaman; 12-30-2012 at 06:11 PM.
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