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    #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.

    Comment


      #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.

      Comment


        #63
        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.

        Comment


          #64
          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.

          Comment


            #65
            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; 30 Dec 2012, 8:54 AM. Reason: I felt like it.

            Comment


              #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?
              T6 complete since 3/21/2012

              Comment


                #67
                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...?
                "Talk without the support of action means nothing..."
                ― DaShanne Stokes

                ***Unite(D) to Fight Paralyses***

                Comment


                  #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.

                  Comment


                    #69
                    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
                    "That's not smog! It's SMUG!! " - randy marsh, southpark

                    "what???? , you don't 'all' wear a poop sac?.... DAMNIT BONNIE, YOU LIED TO ME ABOUT THE POOP SAC!!!! "


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                    Comment


                      #70
                      jsilver

                      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; 30 Dec 2012, 6:11 PM.
                      AS I SIT HERE IN MY CHAIR . I LOOK OUT UPON THE GROUND .I WONDER WILL I EVER GET UP AND WALK A ROUND ??


                      http://justadollarplease.org

                      Comment


                        #71
                        Originally posted by lunasicc42 View Post
                        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

                        I've wondered if it's just semantics, myself; maybe the argument
                        is over the word "scar" vs "gliosis." But they're also debating
                        whether it's necessary to remove sections of spinal cord or not.
                        Wise, to my knowledge, doesn't remove anything from the cord.

                        I just don't understand how both can have successful animal studies
                        with a totally different opinion on a fundamental issue.

                        Comment


                          #72
                          Originally posted by Buck503 View Post
                          I've wondered if it's just semantics, myself; maybe the argument
                          is over the word "scar" vs "gliosis." But they're also debating
                          whether it's necessary to remove sections of spinal cord or not.
                          Wise, to my knowledge, doesn't remove anything from the cord.

                          I just don't understand how both can have successful animal studies
                          with a totally different opinion on a fundamental issue.
                          That's what is confusing and frustrating for me... One is saying regeneration isn't possible without dealing with the scar at chronic time periods and the other is saying, wrong, it is possible and early indications of these human trials seem to point towards just this.
                          Honestly... I don't think there's much more to say until we see at least the next update on the data, hopefully showing explicitly both the white matter growth and the extent of walking, whether posted here or published in a journal... Without the data to help as an arbiter, it's all speculation.

                          Comment


                            #73
                            Have a contused chronic sci at C3/4, use walker for short distances in apartment, feel normal sensation except right toes and somewhat fingers, never had pain after neck healed from fusion surgery, big inflammation response mostly uncurtailed, take no meds, very healthy, spasticity progresses since second year after a second fall after ear surgery (otoslerosis). My question is do I have a scar or much of one? Couldn't autologous stem cell therapy perk up my spinal cord? Thanks!

                            Jan

                            Comment


                              #74
                              NOTE - Been walking with walker ever shorter distances since 5 and a half months at RIC in Chicago. I'm big on nutrition, been a vegan for over a decade, eating natto now for its Vitamin K2 (and protein) and supplementing with lithium orotate.

                              Jan

                              Comment


                                #75
                                Originally posted by ay2012 View Post
                                Anyone else as distressed over this as I am? I know that in science there is room for vigorous disagreement, even between voices as important in spinal cord injury research as Dr.'s Young and Silver...but for them to be so clearly opposed over such a fundamental issue. Has any animal study in a complete, chronic model shown regeneration and/or return of function simply by injecting stem cells into the lesion and without explicitly trying to deal with the "scar"? If yes, then the above statement seems less worrisome. If not, well....
                                Ay,

                                the scar issue has been a source of frustration for me since the beginning.
                                In fact was one of the first reasons I was told for which there is no regeneration after SCI.
                                Soon after my SCI I have found CareCure and I started to hear what Wise thinks about the scar and I have believed him for a while.
                                Nevertheless everytime I have had the opportunity to talk with a doctor or a researcher I have asked what they think about the scar. Turns out, in my exoerience, that most doctors and researchers believe the scar is a problem to deal with in order to get significsant recovery especially in case of severe SCI.
                                The arguments Wise has in support of his position have become weaker year after year at my eyes while arguments I hear that support the idea that the scar is a problem have become stronger especially as the scar has been studied more in details.

                                What is more disturbing to me is that very few researchers have been studing the scar closely (probably because chronic SCI is still considered hopeless by most of the researchers).
                                If the scar had been studied by more people in the past, likely we would be much closer to a real effective therapy to recover functions for people with chronic SCI.

                                Paolo
                                In God we trust; all others bring data. - Edwards Deming

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