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Thread: Jerry Silver and Other Discussion from ChinaSCINet Update

  1. #141
    Quote Originally Posted by GRAMMY View Post
    The video is online now in the educational video library from the Working 2 Walk 2012 Album.
    It's apparently that the man genuinely happy and excited about his work. No a shadow of hypocrisy here.

  2. #142
    Senior Member
    Join Date
    Jan 2009
    Baldwinsville, N.Y.
    Dr. Silvers,
    Thank you for your comments. I will review the information from W2W.
    I appreciate it.
    Best Regards,

  3. #143

    Red face

    - very inspirational. I'm postponing arrangements with my quack salvers. - Where is this tested on humans?
    "It's not the despair, I can handle the despair! It's the hope!" - John Cleese

    Don't ask what clinical trials can do for you, ask what you can do for clinical trials. (Ox)
    Please join me and donate a dollar a day at and copy and paste this message to the bottom of your signature.

  4. #144
    Quote Originally Posted by topperf View Post
    Where is this tested on humans?
    It isn't. This is a research presentation from the 2012 research science symposium. Last year in 2011, Dr. Silver reported his work on restoring breathing for paralyzed diaphragm. You can view that research HERE.

    This year in 2012, he's reporting on the technique and research work in restoring 2 muscles for bladder. The technique isn't tested on humans until it has been perfected and is ready for humans. This is all very new research work being done.

  5. #145
    Quote Originally Posted by jsilver View Post
    While we can't study bowel function in rodents after SCI, because bowel activity in them is little affected by SCI, we are focusing on urinary function which is considerably altered. Indeed, the urinary system seems to be a most accessible system for repair after SCI, since the brainstem nuclei that control urination have a remarkably high intrinsic capacity for long distance regeneration once we give them a bridge across the lesion and the good news is that this can occur even at chronic stages after injury. In addition, we are using either a complete transection or a most severe contusive injury as our models, which is like ASIA A. Please view my 2nd presentation at the recent W2W to see what progress we have made. I have learned that it is coming online soon. I remain highly optimistic that the answer to your question is "yes". We are certainly working as hard and fast as we can to make this a reality.
    Is it true to say that extending these techniqus to restore motor function is a huge challenge because the Cortico Spinal Tract doesn't repair easily? But, with your work and that of the CST Repair Project is there some hope of repair of motor function spinal cord nerves as well?

    many thanks

  6. #146
    Quote Originally Posted by Christopher Paddon View Post
    Is it true to say that extending these techniqus to restore motor function is a huge challenge because the Cortico Spinal Tract doesn't repair easily? But, with your work and that of the CST Repair Project is there some hope of repair of motor function spinal cord nerves as well?

    many thanks
    I do know there's a video coming of a Question and Answer session that Dr. Jerry Silver and Dr. Justin Brown provided at W2W where there was discussions on this topic. It should be up next week.

  7. #147
    Senior Member kate's Avatar
    Join Date
    Jan 2002
    bellevue, wa, usa
    Oh, boy! Those videos are so helpful, Grammy . . . I just spent half the day listening & transcribing so I have accurate & complete information for the w2w book. Such good stuff.

    One thing that's become obvious, listening to them, is how much context is assumed. Part of my task is to create a good baseline -- stuff that all of us trying to advocate for more speed, more money, more emphasis on chronics -- ought to understand. This conversation about the nature of the scar (however it's named) is a good example of how much work remains in that realm.

    ps . . . yo, Dr Silver! You talk very fast.

  8. #148
    Quote Originally Posted by paolocipolla View Post
    Thank you Wise for the publication.

    I see the rats were euthanized within 6 weeks as you say which is a bit too early to call it chronic especially if we are talking about the scar.

    Then I see that even with the 50 mm drop SCI model (which I think is rarely used if ever as a contusion model) rats recover a BBB score of 8 out of 21, which would be probably like an ASIA C human.

    So when you refer to this study to support your position about the scar you could be right if we were talking about the scar present in people ASIA C or D.

    Unfortunatly people with ASIA A likely have a much worse scar problem, which I wish had been studied more rather than just saying the scar is not an issue.


    You should not be equating rat time with human time. This is one of the most common errors that are made by scientists. Rat time is the not the same as human time. I estimate that rat time is at least four times faster than human time. For example, rat heart rate is four time faster. Its metabolism is four times faster. Its drug clearance is four times faster. It reaches a plateau in its recovery curve by 6-8 weeks, whereas it takes a human 6-12 months (depending on the severity of injury). The more severe the injury, the faster one reaches the plateau. So, a 6-week period in a rat is similar to 6 months in human.

    A 50-mm weight drop contusion with the NYU/MASCIS weight drop contusion model results in destruction of over 99% of the white matter at the injury site, including all corticospinal tract axons. The 6-week BBB locomotor scores of rats after a 50-mm contusion plateau at 6.0±0.5 (mean±sem). The injury usually extends into the lumbar gray matter, resulting in flaccid paralysis of the hindlimbs.

    The 6-week BBB locomotor scores of rats after a 25-mm contusion plateaus at 8.0±0.5, also a non-walking score. Over 90% of the spinal cord white matter is destroyed. However, because the injury does not extend into the lumbar gray, the legs are spastic and the spinal cord shows occasional spasms, especially when the rat is using his forelimbs to pull itself along dragging its hindlimbs. A 25-mm weight drop is probably equivalent to an ASIA A with spasticity and spasms.

    The 6-week BBB scores after a 12.5 mm contusion averages about 13.0±0.5, which is a walking score. It is equivalent to an ASIA C. We also have a 6.25 mm weight drop from which rats are paralyzed for several weeks but recover close to normal by 6 weeks. This is probably equivalent to an ASIA D.


  9. #149
    Quote Originally Posted by jsilver View Post
    Oh, but you are wrong here. He does deny that in the absence of fibroblasts in the CNS there is scar. Thus, he denies that gliosis (astrocyte only behavior) can form a barrier. There are no fibroblasts in the brain or spinal cord normally, so in the absence of a penetrating injury that freely allows them into the CNS compartment from the meninges, it has been thought that few fibroblasts enter the CNS. So the astrocytes have taken over the job in the CNS of walling off inflammation. When fibroblasts do enter CNS in large numbers then the scar that is made by astrocytes becomes even more impenetrable because fibroblats produce a myriad of additional inhibitory molecules and the reactive astrocytes wall them off as well with a membranous structure called basal lamina. If you or Wise wish to call what the astrocytes do something other than "scar' that is no problem but you will not be able to communicate with the rest of the world where use of the word scar is more flexible. In the end, the important point is that reactive astrocytes contribute to regeneration failure in the CNS in a big way and they have to be overcome, removed or altered somehow to get regeneration to occur especially at chronic stages. Until data is presented, there is no evidence that UMBCs or lithium are capable of overcoming scar or the inhibitory molecules associated with it.
    As I have said many times before, I don't think that we disagree on the phenomenon. We disagree on the terminology. I believe that the word "scar" should be reserved for situations when fibroblasts are present. In my opinion, the word "gliosis" should be used to refer to tissues where astrocytes have proliferated. I don't even oppose the term "glial scar", as long as it is applied to the situation when fibroblasts have invaded into central nervous tissue and formed a fibrous scar against which glial cells have proliferated.

    The application of the term "glial scar" to any kind of gliosis is not only confusing and can lead to inappropriate medical therapies. There are people here at CareCure who are asking their surgeons to *cut out* glial scars from their spinal cords. I was horrified when I saw Portuguese neurosurgeons cut out a 5 mm by 10 mm chunk of human spinal cords in order to place pieces of nasal mucosa into the spinal cord, saying that they are only removing "glial scar". There are companies thinking that they can cut out the injury site in the spinal cord and put a scaffolding in its place.

    By the way, I did not say that glial cells cannot form any barrier to axonal growth but only that they do not always form that strong a barrier to axonal growth. In 70-80% of contusion injuries of the spinal cord, a loose matrix of astrocytes grow in to the injury site and many axons grow into the injury site. However, in 20-30% of the contusions, the damage is sufficiently severe that cysts have formed and astrocytes do not migrate into the injury site to allow axons to grow in. I also agree with Sofroniew who has noted that astrocytes do help prevent leukocytic invasion into the injury and that elimination of astrocytes is deleterious.

    Your own work strongly argues against the concept that glia form tight physical barriers through which axons cannot penetrate. You have long championed the concept that CSPG plays an important role in preventing axonal growth. Liz Bradbury and many others have shown that digestion of CSPG with chondroitinase will allow axonal sprouting through gliotic tissues in spinal cords. If fact, if there were tight glial barriers that not only block axonal growth but cellular migration, chondroitinase and your PTPsigma inhibitor [1] would not work to regenerate the spinal cord. Finally, your laboratory recently published a study reporting that serotonergic axons show enhanced growth and sprouting within the glial scar [2]. There is clearly no physical barrier to the growth of these axons in the glial scar.

    1. Hawthorne AL, Hu H, Kundu B, Steinmetz MP, Wylie CJ, Deneris ES and Silver J (2011). The unusual response of serotonergic neurons after CNS Injury: lack of axonal dieback and enhanced sprouting within the inhibitory environment of the glial scar. The Journal of neuroscience : the official journal of the Society for Neuroscience 31: 5605-16. Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106, and Department of Neurosurgery, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. Serotonergic neurons possess an enhanced ability to regenerate or sprout after many types of injury. To understand the mechanisms that underlie their unusual properties, we used a combinatorial approach comparing the behavior of serotonergic and cortical axon tips over time in the same injury environment in vivo and to growth-promoting or growth-inhibitory substrates in vitro. After a thermocoagulatory lesion in the rat frontoparietal cortex, callosal axons become dystrophic and die back. Serotonergic axons, however, persist within the lesion edge. At the third week post-injury, 5-HT+ axons sprout robustly. The lesion environment contains both growth-inhibitory chondroitin sulfate proteoglycans (CSPGs) and growth-promoting laminin. Transgenic mouse serotonergic neurons specifically labeled by enhanced yellow fluorescent protein under control of the Pet-1 promoter/enhancer or cortical neurons were cultured on low amounts of laminin with or without relatively high concentrations of the CSPG aggrecan. Serotonergic neurons extended considerably longer neurites than did cortical neurons on low laminin and exhibited a remarkably more active growth cone on low laminin plus aggrecan during time-lapse imaging than did cortical neurons. Chondroitinase ABC treatment of laminin/CSPG substrates resulted in significantly longer serotonergic but not cortical neurite lengths. This increased ability of serotonergic neurons to robustly grow on high amounts of CSPG may be partially due to significantly higher amounts of growth-associated protein-43 and/or beta1 integrin than cortical neurons. Blocking beta1 integrin decreased serotonergic and cortical outgrowth on laminin. Determining the mechanism by which serotonergic fibers persist and sprout after lesion could lead to therapeutic strategies for both stroke and spinal cord injury.
    2. Shen Y, Tenney AP, Busch SA, Horn KP, Cuascut FX, Liu K, He Z, Silver J and Flanagan JG (2009). PTPsigma is a receptor for chondroitin sulfate proteoglycan, an inhibitor of neural regeneration. Science 326: 592-6. Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA. Chondroitin sulfate proteoglycans (CSPGs) present a barrier to axon regeneration. However, no specific receptor for the inhibitory effect of CSPGs has been identified. We showed that a transmembrane protein tyrosine phosphatase, PTPsigma, binds with high affinity to neural CSPGs. Binding involves the chondroitin sulfate chains and a specific site on the first immunoglobulin-like domain of PTPsigma. In culture, PTPsigma(-/-) neurons show reduced inhibition by CSPG. A PTPsigma fusion protein probe can detect cognate ligands that are up-regulated specifically at neural lesion sites. After spinal cord injury, PTPsigma gene disruption enhanced the ability of axons to penetrate regions containing CSPG. These results indicate that PTPsigma can act as a receptor for CSPGs and may provide new therapeutic approaches to neural regeneration.

  10. #150
    Perhaps the most exciting part of the 2nd W2W presentation was the ingenious strategy to do wound preparation of the lesion on these chronic animals. I'm hoping that other scientists working on chronics will take special note of this. I'm surprised by the extent of recovery seen after applying this technique. It provides a fantastic GO signal and may well be critical to future theraputical approaches for chronics. Fantastic work there Jerry. Thanks a million for not giving up on it!

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