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Thread: Jerry Silver and Other Discussion from ChinaSCINet Update

  1. #371
    Quote Originally Posted by ay2012 View Post
    This is a fair enough point Dr. Silver, as are your critiques of the paper, but perhaps then you and Grammy can do away with the argument that some experiment or another was published in a "low impact journal". Anybody in any academic field know there is some politics to publishing so for those of us equipped to talk about the science (you all) maybe we can just focus on the scientific arguments themselves. Thanks, as always, for your comments!
    I agree that it would be better to focus just on the scientific arguments themselves, but that would work well if we were all serious scientists. Unfortunatly many of us get lost when the arguments becomes very scientific, so we can easily buy BS (published or unpublisced).
    So when that happens a more layman arguments might become necessary and usefull to make the truth more esily visible, in my opinion.

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

  2. #372
    Quote Originally Posted by jsilver View Post
    I understand your points about proper use of the BBB rating scale. I've sent several of my students to the Ohio State summer course to learn spinal cord injury techniques where Phil Popovich and Dana McTigue and colleagues do a marvelous job of training students. We have been doing BBB analyses now for a couple of years in the lab so I am getting more familiar with its pros and cons. I'm never impressed anymore with around 2 point improvements in the BBB especially at the low or high end of the scale in terms of potential translational potential. In speaking personally to all of the 3 B's who invented this rating scale (Basso, Breshnahan and Beattie) they suggest a great place to start is at a BBB score of 9-10. This way if a treatment causes harm you can more easily characterize a decline in score and if the treatment is highly potent then you can observe scores that climb above 13. The BBB scale is not linear and this particular part of the scale between 9-13 is especially important because it is more exciting when changes occur in this portion of the range. In this area animals progress form minimal weight bearing steps to fully coordinated walking. I am quite familiar with in vitro assays of neurite elongation and again I caution you that such small changes using low concentrations of inhibitory molecules as substrates worries me. Finally , when I see such small error bars on a plot of BBB scores over time that really concerns me because they used the NYU impactor. We purchased one of these but had quite variable results in terms of our ability to apply highly reproducible impacts to the cord. We had far to much variability in our control animals for my taste in terms of where their BBB scores stabilized over time. One of my students actually did a very careful comparison of the force produced by the NYU impactor versus the computerized Infinite Horizons Device (that we had to purchase at much greater expense) using a mechanical force plate. The data is quite convincing. The Infinite Horizons Device produces far more consistent impacts than does the NYU impactor. So seeing such tiny error bars tells me something is suspicious.
    Thank you dr. Silver for all the very interesting info that you are sharing with the CC community.
    Never before we had the opportunity to learn very rilevant info like the above.

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

  3. #373
    Quote Originally Posted by GRAMMY View Post
    boring outdated acute research theory
    From 2011:
    Our recent research suggests that certain NSAIDs including ibuprofen suppress intracellular RhoA signal and improve significant axonal growth and functional recovery following axonal injury in the CNS.
    Importantly, we evaluated RhoA inhibition with NSAIDs on axon structural alterations in the chronic stage 4–6 weeks after SCI and observed improved myelination around the lesioned spinal cord. Although we could not exclude possible protective effects of RhoA- inhibiting NSAIDs to axonal cylinders, our results suggest that increased survival of OLGs following RhoA suppression with Ibu or Ind attenuates demyelination of spinal cord axons and facilitates remyelination of spared and/or regenerated axons around the lesion, thus enhancing axonal myelination around the lesion.
    An acute study but hardly boring.
    Last edited by crabbyshark; 02-04-2013 at 07:41 PM. Reason: added link

  4. #374
    Quote Originally Posted by jsilver View Post
    My favorite part of the paper:

    "We recently reported that pain reliever ibuprofen improved axon
    growth and functional recovery in SCI rodents when applied at a
    dose of 60 mg/kg/d, which is a higher dose than that used clinically
    as a cyclooxygenase inhibitor (Fu et al., 2007)."

    Amazing isn't it that this ended up in a good journal.
    Quote Originally Posted by jsilver View Post
    As Grammy points out they've already reported the most bogus observation of all suggesting that ibuprophen might be therapeutic; really.
    From the Journal of Neurotrauma:
    Ibuprofen Enhances Recovery from Spinal Cord Injury by Limiting Tissue Loss and Stimulating Axonal Growth
    Last edited by crabbyshark; 02-04-2013 at 06:33 PM.

  5. #375
    Crabbyshark, why do you keep quoting papers at random pretending that you know what you're talking about? Do you seriously believe that ibuprofen is some sort of treatment for sci?

  6. #376
    Quote Originally Posted by Christopher Paddon View Post
    Crabbyshark, why do you keep quoting papers at random pretending that you know what you're talking about? Do you seriously believe that ibuprofen is some sort of treatment for sci?
    Scientists seem to think so.
    Nonsteroidal anti-inflammatory drugs (NSAIDs) are extensively used to relieve pain and inflammation in humans via cyclooxygenase inhibition. Our recent research suggests that certain NSAIDs including ibuprofen suppress intracellular RhoA signal and improve significant axonal growth and functional recovery following axonal injury in the CNS. Several NSAIDs have been shown to reduce generation of amyloid-beta42 peptide via inactivation of RhoA signal, supporting potent RhoA-repressing function of selected NSAIDs. In this report, we demonstrate that RhoA-inhibiting NSAIDs ibuprofen and indomethacin dramatically reduce cell death of oligodendrocytes in cultures or along the white matter tracts in rats with a spinal cord injury. More importantly, we demonstrate that treatments with the RhoA-inhibiting NSAIDs significantly increase axonal myelination along the white matter tracts following a traumatic contusion spinal cord injury. In contrast, non-RhoA-inhibiting NSAID naproxen does not have such an effect. Thus, our results suggest that RhoA inactivation with certain NSAIDs benefits recovery of injured CNS axons not only by promoting axonal elongation, but by enhancing glial survival and axonal myelination along the disrupted axonal tracts. This study, together with previous reports, supports that RhoA signal is an important therapeutic target for promoting recovery of injured CNS and that RhoA-inhibiting NSAIDs provide great therapeutic potential for CNS axonal injuries in adult mammals.

  7. #377
    Senior Member lynnifer's Avatar
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    Please don't take this the wrong way, but after that - I"ll be skipping over your posts. Seriously ...
    Roses are red. Tacos are enjoyable. Don't blame immigrants, because you're unemployable.

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  8. #378
    I am surprised to hear your opinion of the Horizon device. The consistency of spinal cord injury is based on many factors, including the device used to injure the spinal cord. The Impactor delivers the most precise and monitored impacts of any device (±1%). When carried out by an experienced surgeon following the model, it produces very small standard errors of means for BBB scores, white matter sparing, and impact parameters. I wish that you had told me of the difficulties that you student had with the model.

    Wise.

    Quote Originally Posted by jsilver View Post
    I understand your points about proper use of the BBB rating scale. I've sent several of my students to the Ohio State summer course to learn spinal cord injury techniques where Phil Popovich and Dana McTigue and colleagues do a marvelous job of training students. We have been doing BBB analyses now for a couple of years in the lab so I am getting more familiar with its pros and cons. I'm never impressed anymore with around 2 point improvements in the BBB especially at the low or high end of the scale in terms of potential translational potential. In speaking personally to all of the 3 B's who invented this rating scale (Basso, Breshnahan and Beattie) they suggest a great place to start is at a BBB score of 9-10. This way if a treatment causes harm you can more easily characterize a decline in score and if the treatment is highly potent then you can observe scores that climb above 13. The BBB scale is not linear and this particular part of the scale between 9-13 is especially important because it is more exciting when changes occur in this portion of the range. In this area animals progress form minimal weight bearing steps to fully coordinated walking. I am quite familiar with in vitro assays of neurite elongation and again I caution you that such small changes using low concentrations of inhibitory molecules as substrates worries me. Finally , when I see such small error bars on a plot of BBB scores over time that really concerns me because they used the NYU impactor. We purchased one of these but had quite variable results in terms of our ability to apply highly reproducible impacts to the cord. We had far to much variability in our control animals for my taste in terms of where their BBB scores stabilized over time. One of my students actually did a very careful comparison of the force produced by the NYU impactor versus the computerized Infinite Horizons Device (that we had to purchase at much greater expense) using a mechanical force plate. The data is quite convincing. The Infinite Horizons Device produces far more consistent impacts than does the NYU impactor. So seeing such tiny error bars tells me something is suspicious.

  9. #379
    anti inflammatories are not going to cure chronic sci

    There have been a few ways suggested to decrease the inflammation very soon after the accident for example hyperbaric oxygen, anti inflammatories, steroids but how many have proved to be of any practical use?

    but I'll wager everyone on this forum has a chronic injury so these acute studies that keep getting posted are not of much relevance

    Scientists may test something in an acute situation primarly because it may be easier and then move on to a chronic situation more relevant to human injuries but I can't imagine ibuprofen will be of much use.

    But I'm no scientist - just my thoughts

  10. #380
    Christopher,

    What the authors found was that these NSAID's appear to block rho. Those results were very clear. I don't share Jerry's skepticism of all the results in the paper. Nor did the peer reviewers of the paper share his views. Finally, you should know that the most effective way to reduce stroke in people is a baby aspirin a day.

    Wise.

    Quote Originally Posted by Christopher Paddon View Post
    anti inflammatories are not going to cure chronic sci

    There have been a few ways suggested to decrease the inflammation very soon after the accident for example hyperbaric oxygen, anti inflammatories, steroids but how many have proved to be of any practical use?

    but I'll wager everyone on this forum has a chronic injury so these acute studies that keep getting posted are not of much relevance

    Scientists may test something in an acute situation primarly because it may be easier and then move on to a chronic situation more relevant to human injuries but I can't imagine ibuprofen will be of much use.

    But I'm no scientist - just my thoughts

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