Announcement

Collapse
No announcement yet.

Jerry Silver and Other Discussion from ChinaSCINet Update

Collapse
X
 
  • Filter
  • Time
  • Show
Clear All
new posts

    #76
    Originally posted by Solan View Post
    Good point
    Solan,

    could you check with the spinal unit in Oslo to see if/when they are planning to start clinical trials with UCB cells?

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

    Comment


      #77
      If Dr. Silver is correct, then we are screwed. I am a dentist. I have watched surgery in my residency. It is barbaric and damaging to tissue. If you go into a spinal cord and remove anything, you will be worse or die. The access and violation of the integrity tissues and of millions of axons will be worse then your original injury. You want to re recover again? If their was an antibody that could remove this "SCAR TISSUE" then maybe. Ripping muscle tendons an every layer of the spinal cord exposing it to infection and foreign cells and bacteria in unfathomable to me.
      This is after ripping everything out to get to the spinal cord.
      http://www.youtube.com/watch?v=HoWWRQfWYTo
      Han: "We are all ready to win, just as we are born knowing only life. It is defeat that you must learn to prepare for"

      Comment


        #78
        Originally posted by Fly_Pelican_Fly View Post
        Basic science is very different to translational science which in turn is very different to a clinical study. You cannot expect a single researcher to be responsible for a therapy from discovery to bedside. To expect that is ridiculous.

        Also note that the nature of beast (science can be glacial) is that any science at clinical study stage will likely be objectively analysed by researchers that are working upon lines of science that are one or two generations down the line at basic/translational stages.

        If and when Ch'ase gets to the clinic, Hans Keirstead or Murray Blackmore may debate the weaknesses of the enzyme or the viral vector delivery. If PTEN/SOCS3 gets to the clinic, Reggie Edgerton may question whoever the principal investigator is for the trial about the type of rehabilitative component being used in the trial.

        May the debate continue - it's healthy. It happens at scientific meetings. It happens at symposiums. Why shouldn't it happen here? If we suppress it, more of our well-informed advocates will leave this forum as they have done recently.
        .....
        In God we trust; all others bring data. - Edwards Deming

        Comment


          #79
          Jerry,

          I am aware of Michael Sofroniew's studies. In fact, the thrust of his laboratory's work is very much in line with our own. For example, in an important 2004 paper (abstract below), they reported that mild and moderate stab wounds of the spinal cord do not produce much tissue loss but severe crush or contusion injuries produce areas that are devoid of astrocytes. They concluded that reactive astrocytosis is good and that reactive astrocytes protect tissue and preserve function after spinal cord injury. We also consider these astrocytes to be good for the spinal cord.

          I have looked at hundreds of contused rat spinal cords. Many axons enter the injury site from surrounding tissues. If there really were a barrier to axons entering the injury site, why are we seeing all these axons? I am not saying that glial scars do not exist. I just don't think that it is present in most contused spinal cords. In very severe spinal cord contusions where there is massive tissue loss and cells invading from outside the central nervous system will result in a cavity. Reactive glial cells can and do surround such cavities. Glial scars do form when one does a hemisection or transection of the spinal cord without carefully closing the dura. However, in a majority of 12.5 mm and 25.0 mm weight drop contusions of the rat spinal cord, we simply do not see a tight glial barrier that you describe.

          Finally, we have seen many axons entering the injury site after injury. In 2001, Hill, et al. did a followup study of the kinds of axons that enter the injury site. Yes, I am aware that they call the injury site a "cavity" but they also characterize this "cavity" as being filled with a loose matrix of tissue and that even corticospinal tract (CST) axons penetrate into the "lesion matrix" over long periods of as long as 8 months and that reticulospinal tracts penetrate into the matrix over that same period of time.

          Wise.
          1. Faulkner JR, Herrmann JE, Woo MJ, Tansey KE, Doan NB and Sofroniew MV (2004). Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci 24: 2143-55. Department of Neurobiology, University of California, Los Angeles, California 90095-1763, USA. Reactive astrocytes are prominent in the cellular response to spinal cord injury (SCI), but their roles are not well understood. We used a transgenic mouse model to study the consequences of selective and conditional ablation of reactive astrocytes after stab or crush SCI. Mice expressing a glial fibrillary acid protein-herpes simplex virus-thymidine kinase transgene were given mild or moderate SCI and treated with the antiviral agent ganciclovir (GCV) to ablate dividing, reactive, transgene-expressing astrocytes in the immediate vicinity of the SCI. Small stab injuries in control mice caused little tissue disruption, little demyelination, no obvious neuronal death, and mild, reversible functional impairments. Equivalent small stab injuries in transgenic mice given GCV to ablate reactive astrocytes caused failure of blood-brain barrier repair, leukocyte infiltration, local tissue disruption, severe demyelination, neuronal and oligodendrocyte death, and pronounced motor deficits. Moderate crush injuries in control mice caused focal tissue disruption and cellular degeneration, with moderate, primarily reversible motor impairments. Equivalent moderate crush injuries combined with ablation of reactive astrocytes caused widespread tissue disruption, pronounced cellular degeneration, and failure of wound contraction, with severe persisting motor deficits. These findings show that reactive astrocytes provide essential activities that protect tissue and preserve function after mild or moderate SCI. In nontransgenic animals, crush or contusion SCIs routinely exhibit regions of degenerated tissue that are devoid of astrocytes. Our findings suggest that identifying ways to preserve reactive astrocytes, to augment their protective functions, or both, may lead to novel approaches to reducing secondary tissue degeneration and improving functional outcome after SCI.
          2. Hill CE, Beattie MS and Bresnahan JC (2001). Degeneration and sprouting of identified descending supraspinal axons after contusive spinal cord injury in the rat. Exp Neurol 171: 153-69. Department of Neuroscience, The Ohio State University, Columbus, Ohio 43210, USA. Contusive spinal cord injury (SCI) results in the formation of a chronic lesion cavity surrounded by a rim of spared fibers. Tissue bridges containing axons extend from the spared rim into the cavity dividing it into chambers. Whether descending axons can grow into these trabeculae or whether fibers within the trabeculae are spared fibers remains unclear. The purposes of the present study were (1) to describe the initial axonal response to contusion injury in an identified axonal population, (2) to determine whether and when sprouts grow in the face of the expanding contusion cavity, and (3) in the long term, to see whether any of these sprouts might contribute to the axonal bundles that have been seen within the chronic contusion lesion cavity. The design of the experiment also allowed us to further characterize the development of the lesion cavity after injury. The corticospinal tract (CST) underwent extensive dieback after contusive SCI, with retraction bulbs present from 1 day to 8 months postinjury. CST sprouting occurred between 3 weeks and 3 months, with penetration of CST axons into the lesion matrix occurring over an even longer time course. Collateralization and penetration of reticulospinal fibers were observed at 3 months and were more extensive at later time points. This suggests that these two descending systems show a delayed regenerative response and do extend axons into the lesion cavity and that the endogenous repair can continue for a very long time after SCI.
          Last edited by Wise Young; 30 Dec 2012, 11:07 PM.

          Comment


            #80
            Originally posted by paolocipolla View Post
            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
            Most of the studies of "glial scar" have been done in animal models where penetrating wounds of the spinal cord have been done on the spinal cord. A lot of people are pontificating on glial scars without having studied spinal cord contusions, which constitute a majority of human spinal cord injuries.

            Wise.

            Comment


              #81
              Originally posted by jsilver View Post
              Learn from yesterday, live for today, hope for tomorrow. The important thing is not to stop questioning.
              Albert Einstein


              I agree, do others?
              Soon after my SCI my understanding of SCI research was very poor, so I had relatively few questions, but as my understanding of it gets better the number of questions I have keep growing and I have seen the same happen to others.
              Questions are essential in any learning process, but also for agitating the field to make faster progress happen etc..

              So I agree with Albert based on my personal experience

              Paolo
              Last edited by paolocipolla; 30 Dec 2012, 11:12 PM.
              In God we trust; all others bring data. - Edwards Deming

              Comment


                #82
                Originally posted by jsilver View Post
                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
                It will be 20 years at least at that stage to a treatment. Notice no motor or sensory function.

                happy new years except for us......
                Han: "We are all ready to win, just as we are born knowing only life. It is defeat that you must learn to prepare for"

                Comment


                  #83
                  [QUOTE=Wise Young;1631505]

                  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.
                  What would you do in that case? Leave the fibrous scar there and just inject UCB cells?

                  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.
                  ..but that was acute SCI..

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

                  Comment


                    #84
                    Originally posted by Wise Young View Post
                    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.
                    Wise,

                    I am very interested in understanding better the MASCIS study.

                    How long after the injury were the animals sacrfied?
                    How much BBB score did the rats that got 25mm weight drop recover?
                    How much the rats that got 50mm weight drop?

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

                    Comment


                      #85
                      Originally posted by paolocipolla View Post
                      Wise,

                      I am very interested in understanding better the MASCIS study.

                      How long after the injury were the animals sacrfied?
                      How much BBB score did the rats that got 25mm weight drop recover?
                      How much the rats that got 50mm weight drop?

                      Paolo
                      I attach a reprint of the paper. If I remember correctly, most of the rats were euthanized at 6 weeks after injury. The BBB scores of the rats with 25 mm weight drop injuries averaged about 8 (non-walking). We studied 3 contusion levels, i.e. the 12.5, 25.0, 50.0 mm, about 150-200 rats per group.

                      Wise.

                      Comment


                        #86
                        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?
                        It's an interesting approach and in case it works it can be very usefull if not essential to repair the spinal cord.
                        The idea is not new, but perhaps it is now duable as Hans explained.
                        Few years ago I have discussed this approach with a young german neuroscientist.. He was presenting a poster of how he generated astrocites from neural stem cell. I asked him what about reversing the process in the case of the SCI glial scar? He was intrigued by the question and he speculated that it could have been possible in the future to do that.

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

                        Comment


                          #87
                          Originally posted by paolocipolla View Post
                          Solan,

                          could you check with the spinal unit in Oslo to see if/when they are planning to start clinical trials with UCB cells?

                          Paolo
                          I just spoke to Oslo for you and they said that you should plan your own trial Paulo and start harassing yourself instead.
                          Originally posted by paolocipolla
                          Moe,

                          I... don't care about what I think ... you should just ignore my posts.

                          I don't understand ... words.

                          Paolo

                          Comment


                            #88
                            Originally posted by paolocipolla View Post
                            Originally posted by Wise Young View Post

                            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.
                            What would you do in that case? Leave the fibrous scar there and just inject UCB cells?

                            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.
                            ..but that was acute SCI..

                            Wise.
                            Paolo,

                            Penetrating wounds of the spinal cord are relatively rare. For example, we did not see any case of a penetrating or transecting wound of the spinal cord in 41 ASIA A patients that we transplanted cells into so far, 28 of which are chronic and 13 were subacute. All the spinal cord appear intact from the outside. We inject the cells into the spinal cord surrounding the injury site, into the dorsal root entry zones above and below the injury site.

                            Yes, Liu, et al. 2010 did assess regeneration in "acute" spinal cord injury, in the sense that the rats already had PTEN deleted before they were injured. On the other hand, the regeneration across the injury site took a long time. Kai Liu had to wait 6-8 weeks before he saw the axons grow across the injury site. In rat and mouse time, each week is equal to about a month. If a glial scar formed, it should have been there within 2-3 weeks.

                            It seems to me that the burden of proof should lie on those people claiming that there is a "scar" that obstructs axonal growth rather than on people who don't see any scar there and are finding axons that grow into the contusion site. If a scar is there and is truly blocking axonal growth in contused spinal cords, why are we seeing so many axons crossing the injury site in the chronically injured spinal cord?

                            Wise.
                            Last edited by Wise Young; 31 Dec 2012, 3:57 AM.

                            Comment


                              #89
                              I know a man who was injured at c5 that regained almost all function after nearly 18 years after injury. 12 years after his injury his hands and remaining arm muscles woke up out of nowhere, 3-4 years after that was his legs. Nowadays he barely uses a cane. He works with my mom as a maintenance guy and never met anyone else as hyperactive...

                              He keeps my hopes up, having this 'scar' didn't seem to block anything for him, fortunately and lucky for him his 'fibers' found its way to reconnect on their own.

                              His advice to me was "never tell you mind that it's over, keep positive thoughts along with a positive attitude"

                              To me I'm convinced with research there will be a way the fibers will reconnect regardless if this 'scar' is there or not.

                              Let’s keep our hopes up and may the year 2013 give us good research results.
                              "Talk without the support of action means nothing..."
                              ― DaShanne Stokes

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

                              Comment


                                #90
                                very interesting. Have they done MRIs on him before and after to determine how he regained his function.

                                Comment

                                Working...
                                X