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Working2Walk 2011 features Dr. Jerry Silver!

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    #46
    Jerry, may I ask what is perhaps an obvious question?, Do your grafts actually leave the spinal cord and than reenter, similar to Albert Aguayo's experiment in 1982? (I remember that when I had my accident). Would this be a safe long term solution with nerves outside the dura?

    Secondly, I wonder if you have had any success with sensory nerves? You seem to have had success in almost every function.

    Comment


      #47
      Originally posted by Christopher Paddon View Post
      Jerry, may I ask what is perhaps an obvious question?, Do your grafts actually leave the spinal cord and than reenter, similar to Albert Aguayo's experiment in 1982? (I remember that when I had my accident). Would this be a safe long term solution with nerves outside the dura?

      Secondly, I wonder if you have had any success with sensory nerves? You seem to have had success in almost every function.

      Dear Christopher,

      In our 2 published papers (J Neurosci 2006 / Nature 2011) we used grafts that targeted motor pathways specifically. The graft is inserted into the cord on the rostral (towards the brain) side of the lesion and then goes outside the dura to bypass the lesion and is then inserted again through the dura far caudally ( towards the tail) near the vicinity of the motor neurons that we are interested in re-innervating with regenerated nerve fibers. This would be OK in humans since the nerve graft gets tightly adhered to the dura and would be covered with the spine. The graft could also be routed under the dura. However, in our most recent work using a complete transection lesion (shown just last week at SFN, see Yu-Shang Lee et al SFN abstracts see below) we used multiple grafts that bridged the lesion entirely within the cord itself. Remarkably, we have learned that if we wait long enough ( 6 months) many axons (all from the brainstem and local circuit propriospinal neurons from just above the lesion) can regenerate remarkably well through and then well past the lesion and, importantly, all the way down to the end of the spinal cord. Such regeneration has brought back substantial return of urinary function. We have not yet examined sensory function but this new graft strategy could, indeed, allow for sensory regeneration.
      I would also like to take the opportunity here to comment on the recent Geron decision to exit their stem cell trials which were based on the pioneering work of Hans Kierstead. I would very much like to stress that these trials may well have been ill designed from the outset. While we are all upset by this decision which was apparently based on a corporate greed mentality, if one follows closely Han's work, you will see that in his more recent results using the same cells he is moving away from the idea that his cells were restoring function based solely on re-myelination. Rather he is now suggesting that they were acting by neuroprotection. This leaves the Anderson/Cummings cells as the major stem cell type that could still potentially restore some function via re-myelination. There are myriads of other types of stem cells that can act via neuroprotective mechanisms so the loss of the Geron cells is NO BIG DEAL. Also, in Han's early paper he showed clearly that his cells could not restore function at even sub-chronic stages. Thus, for neuroprotection, I would suggest that we need to get stem cells into the injured cord ASAP (in the ambulance via I.V. if possible). We shouldn't be waiting around 1-2 weeks since much secondary damage has already occurred. There is still no clear cut example of stem cells having a reparative capacity on SCI at long chronic time points.


      Nerve Regeneration and Improvement in Urodynamics and External Urethral Sphincter activity in Complete Spinal Cord Transected Rats Treated with a Peripheral Nerve Graft, Acidic Fibroblast Growth Factor, and ChondroitinaseABC

      1,2Y.-S. Lee, 3H-H. Jiang, 4M. DePaul, 1,2C.-Y. Lin, 3M. S. Damaser,2V. W. Lin, and 4J. Silver
      Departments of 1Neurosciences and 2Physical Med & Rehab and 3Department of Biomedical Engineering, Cleveland Clinic Foundation. 4Department of Neuroscience, Case Western Reserve University.

      Relatively few studies have focused on central neuronal regeneration with the goal of fostering recovery of efficient micturition. The effects of peripheral nerve grafts (PNG) and acidic fibroblast growth factor (aFGF) combined with ChondroitinaseABC (ChABC) on bladder reflexes after complete spinal cord transection (ST) at T8 in adult rats were studied. Rats were divided randomly into six groups: (1) Sham control (laminectomy only), (2) ST only, (3) ST+PNG, (4) ST+aFGF+ChABC, (5) ST+PNG+aFGF, (6) ST+PNG+aFGF+ChABC. Two injections of ChABC were made near the rostral and caudal stumps of the spinal cord. Urodynamics and external urethral sphincter electromyogram (EMG) activity were recorded six months after injury. Anterograde tracing was used to evaluate axonal regeneration. Urodynamic data in the ST+PNG+aFGF+ChABC animals was markedly improved beyond that in the other four injury groups. The ST+PNG+aFGF+ChABC group also showed significant shorter time to void and significantly improved patterns of high frequency oscillations of detrusor contractions (bladder pressure tracings) during voiding than the other four injury groups. This indicates that the PNG+aFGF+ChABC group did not need to store large volumes of urine (less bladder incontinence and distention) to void and developed better coordination between detrusor and sphincter activity, which is closer to a normal pattern. The ST+PNG+aFGF+ChABC group also displayed higher amplitudes and bursting rates of sphincter EMG activity than the other injured animals. The improvement in urodynamics and EMG disappeared after spinal cord re-transection in the ST+PNG+aFGF+ChABC group, suggesting that supraspinal regeneration is critical for recovery. Anterograde tracing studies revealed more regenerated fibers in the distal end of the spinal cord in the ST+PNG+aFGF+ChABC group. The improvements in bladder reflexes might have been due to newly formed supraspinal control via nerve regeneration.

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        #48
        Thanks Jerry - it sounds encouraging

        Stem cells are expected to do everything by the general public I think. And often things are called stem cells which aren't, just to make them sound more impressive or just from ignorance, I don't know. OEG cells are an example.

        Comment


          #49
          Originally posted by GRAMMY View Post
          My prayers are with you!
          Why are you posting videos of lectures from the conference by only one lecture each month? Are you lacking the technology to post all lectures at once (or is it a pr gimmic stunt)? And if you cant do that ‘simple trick’ how do you imagine to fix SCI? One axon each month would be great, but compared to 300 millions one can fall asleep nevertheless how exiting

          Comment


            #50
            Originally posted by Leif View Post
            Why are you posting videos of lectures from the conference by only one lecture each month? Are you lacking the technology to post all lectures at once (or is it a pr gimmic stunt)? And if you cant do that ‘simple trick’ how do you imagine to fix SCI? One axon each month would be great, but compared to 300 millions one can fall asleep nevertheless how exiting
            I apologize Leif, I do not have the technology to fix SCI. (But, then obviously YOU can't imagine how to do that 'simple trick' either!)

            I've posted a link to the video page as they come online (4 in a month) as a courtesy to others that were not able to attend. I'm sorry you cannot appreciate everyones efforts to help the sci community. The videographer wasn't the greatest and there are difficulties with enhancing the audio on many of the presentations. I know people are working on this and doing the very best they can.

            I'll be sure to avoid posting future notices each week to the link as the video's are brought online from Working 2 Walk so you needn't worry about one axon or exiting afterall ... I do feel that everyone but you actually benefitted and appreciated it.
            Last edited by GRAMMY; 23 Nov 2011, 10:36 PM.
            http://spinalcordresearchandadvocacy.wordpress.com/

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              #51
              Grammy,
              What you bring to this site is very much appreciated. I read most of your threads because they are usually very helpful and informative. Thank you for letting us know when the videos are available and for providng us with the link, this has been very helpful. Please continue to do so.

              Geoman
              "Wheelie Wanna Walk!"

              Comment


                #52
                Well thank you Geoman! I'm happy that you are appreciative of the videos and what information I'm able to find to help everyone out (even though I'm not a neuroscientist) LOL We'll keep pushing forward and doing the best we possibly can. Stay well Geoman!
                http://spinalcordresearchandadvocacy.wordpress.com/

                Comment


                  #53
                  Originally posted by Leif View Post
                  Why are you posting videos of lectures from the conference by only one lecture each month? Are you lacking the technology to post all lectures at once (or is it a pr gimmic stunt)? And if you cant do that ‘simple trick’ how do you imagine to fix SCI? One axon each month would be great, but compared to 300 millions one can fall asleep nevertheless how exiting
                  Leif, you are a good-natured nice chap, don't pretend to be wicked Viking.

                  Comment


                    #54
                    Originally posted by Leif View Post
                    Why are you posting videos of lectures from the conference by only one lecture each month? Are you lacking the technology to post all lectures at once (or is it a pr gimmic stunt)? And if you cant do that ‘simple trick’ how do you imagine to fix SCI? One axon each month would be great, but compared to 300 millions one can fall asleep nevertheless how exiting
                    Leif,

                    I am hoping that soon you will organize in "Noway" an European W2W so you can show us that NoRway is the best in everithing!

                    Be nice or I tell it to your sister

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

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