Thread: Stephen Davies Update

  1. #1341
    Thank everybody here for the great discussion. I want to interject here a possible explanation for why Stephen Davies studied the spinal cord at 12 days after contusion rather than longer periods.

    After one does the laminectomy to expose the spinal cord, does the contusion (drop a weight onto the spinal cord), and then closes the skin over the laminectomy site, one must be careful to place a pinch of subcutaneous fat over the dura. Otherwise, when the laminectomy site closes (and it does close over in rats in about 2 weeks), the scar (yes, it is real fibrous scar) will stick to the dura. When one then tries to re-expose the laminectomy site several weeks after injury to administer therapies to the spinal cord (or inject cells), this usually tears the dura and this affects the recovery of the animal. This little trick is what allows investigators to open the spinal cord more than 2 weeks after injury and treat the spinal cord. Not knowing this trick, I believe, is one reason why most researchers in the field have stuck to 12-14 days as the latest treatment time when they use the contusion model in rats.

    I have held four 3-day workshop a year (teaching about 50-100 scientists each year) to do the rat spinal cord contusion model for over 15 years. There are hundreds of little details of doing the contusion model and taking care of the animals that are essential for chronic spinal cord injury studies. I have taught these details of the surgery, as well as proper BBB scoring of rats and care of chronic spinal cord injury to over 1000 investigators over the past two decades.

    Wise.
    Last edited by Wise Young; 01-24-2013 at 06:39 AM.

  2. #1342
    Quote Originally Posted by Wise Young View Post

    I have held four 3-day workshop a year (teaching about 50-100 scientists each year) to do the rat spinal cord contusion model for over 15 years. There are hundreds of little details of doing the contusion model and taking care of the animals. I have taught these details of the surgery, as well as proper BBB scoring of rats and care of chronic spinal cord injury to over 1000 investigators over the past two decades.

    Wise.
    I bet Paolo could teach you a thing or two though...Sorry, couldn't help myself!

    Clayton
    "Wheelie Wanna Walk!"

  3. #1343
    Quote Originally Posted by Charles Hansen View Post
    Yes, I freely admit not keeping up with the latest research by anyone, including Dr. Davies. I have asked several times for links to any research that shows more promise than the papers presented by Dr. Davies but not one poster has give a link.
    There are some threads outside of this one. And there is also a search function at the top. Alternatively you could start by watching some of the W2W videos from 2011 and 2012. There should be enough there.

  4. #1344
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    Quote Originally Posted by Fly_Pelican_Fly View Post
    There are some threads outside of this one. And there is also a search function at the top. Alternatively you could start by watching some of the W2W videos from 2011 and 2012. There should be enough there.
    In order for that to happen somebody will need to invent a TV that works when it's buried in the sand.

  5. #1345
    From glorious days -
    what have happened in the meantime

    rats rats rats rats
    www.MiracleofWalk.com

    Miracles are not contrary to nature, but only contrary
    to what we know about nature
    Saint Augustine

  6. #1346
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    I saw this online. Dr. Davies has moved to the Florey Institute in Australia.

    Dr. Stephen Davies is a principal research fellow and heads the spinal research laboratory at the Florey. He is an internationally recognized research scientist who has devoted his scientific career to gaining a better understanding of why axon regeneration fails in the mammalian central nervous system (CNS) and the development of new technologies for repairing the injured or diseased brain and spinal cord.

    Dr. Davies completed his doctoral thesis in neurobiology studying axon growth in the adult mammalian CNS at the National Institute for Medical Research, Mill Hill, London which was awarded by University College London in 1996. It was upon moving from London to Case Western Reserve University in Cleveland, Ohio as a postdoctoral fellow that Dr. Davies initiated a series of adult neuron to adult CNS transplantation experiments that fundamentally changed the scientific community’s understanding of the role of scar tissue in preventing axon regeneration in the traumatically injured adult brain and spinal cord. He was recruited as an assistant professor to Baylor College of Medicine, Texas in 2000, and later in 2007 to the University of Colorado, Denver as an Associate Professor with appointments in Neurosurgery, Neurology and Neurosciences. It was during his tenures in Texas and Colorado that Dr. Davies focused on the development of two complementary approaches to repairing the injured adult CNS. The first was a novel stem cell based technology for making specific subtypes of beneficial astrocytes (a major CNS support cell) suitable for repairing the injured adult central nervous system. The second was to investigate the use of a small leucine rich proteoglycan called Decorin as a means of promoting regeneration and plasticity of neural circuits within the axon growth inhibitory environment of the injured adult CNS. Dr. Davies was awarded the American Spinal Injury Association prize for breakthrough in spinal cord injury research for his studies with Decorin. In 2014 Dr. Davies was recruited to the Florey where he is continuing the development of Decorin and stem cell-derived human astrocytes for use in treating a variety of neurological disorders with a particular interest in chronic spinal cord injury. Dr. Davies research interests lie in understanding the cell and molecular biology regulating CNS repair.

  7. #1347
    Quote Originally Posted by Roger View Post
    I saw this online. Dr. Davies has moved to the Florey Institute in Australia.
    Decorin! Those were the days...

  8. #1348
    Quote Originally Posted by quadfather View Post
    Decorin! Those were the days...

    Decorin blocks scarring and cystic cavitation in acute and induces scar dissolution in chronic spinal cord wounds.

    Ahmed Z1, Bansal D2, Tizzard K2, Surey S2, Esmaeili M2, Gonzalez AM2, Berry M2, Logan A2.


    Abstract

    In the injured central nervous system (CNS), transforming growth factor (TGF)-β1/2-induced scarring and wound cavitation impede axon regeneration implying that a combination of both scar suppression and axogenic treatments is required to achieve functional recovery. After treating acute and chronic dorsal funicular spinal cord lesions (DFL) in adult rats with the pan-TGF-β1/2 antagonist Decorin, we report that in: (1), acute DFL, the development of all injury parameters was significantly retarded e.g., wound cavity area by 68%, encapsulation of the wound by a glia limitans accessoria (GLA) by 65%, GLA basal lamina thickness by 94%, fibronectin, NG2 and Sema-3A deposition by 87%, 48% and 48%, respectively, and both macrophage and reactive microglia accumulations by 60%; and (2), chronic DFL, all the above parameters were attenuated to a lesser extent e.g., wound cavity area by 11%, GLA encapsulation by 25%, GLA basal lamina thickness by 31%, extracellular fibronectin, NG2 and Sema-3A deposition by 58%, 22% and 29%, respectively, and macrophage and reactive microglia accumulations by 44%. Moreover, in acute and chronic DFL, levels of tissue plasminogen activator (tPA) were raised (by 236% and 482%, respectively), as were active-MMP-2 (by 64% and 91%, respectively) and active-MMP-9 (by 122% and 18%, respectively), while plasminogen activator inhibitor-1 (PAI-1) was suppressed (by 56% and 23%, respectively) and active-TIMP-1 and active TIMP-2 were both lower but only significantly suppressed in acute DFL (by 56 and 21%, respectively). These findings demonstrate that both scar tissue mass and cavitation are attenuated in acute and chronic spinal cord wounds by Decorin treatment and suggest that the dominant effect of Decorin during acute scarring is anti-fibrogenic through suppression of inflammatory fibrosis by neutralisation of TGF-β1/2 whereas, in chronic lesions, Decorin-induction of tPA and MMP (concomitant with reduced complimentary levels of TIMP and PAI-1) leads to dissolution of the mature established scar by fibrolysis. Decorin also promoted the regeneration of similar numbers of axons through acute and chronic wounds. Accordingly, intrathecal delivery of Decorin offers a potential translatable treatment for scar tissue attenuation in patients with spinal cord injury.

    Does this mean Decorin is good again? lol

  9. #1349
    Quote Originally Posted by Roger View Post
    [FONT=Arial]I saw this online. Dr. Davies has moved to the Florey Institute in Australia.
    FONT]
    Guys keep your eyes out for Melbourne in terms of chronic SCI research. Here we now have Dr. Davies and his team at the Florey, along with the work that StepAhead is doing (I am actually on the board of that organisation). It will be interesting to watch the competition between these two groups. As for the people that have all of a sudden think that Decorin does not work, all I will say is that Dr.Davies main focus right now is on his Decorin work, and if people have seen his result with astrocytes, you only need to think a little logically to figure out why he is focusing on something else when astrocytes showed such good results! I can't say anything else...
    Last edited by zoki83; 01-15-2015 at 12:27 PM.

  10. #1350
    Quote Originally Posted by Fly_Pelican_Fly View Post
    No offence Charles, but you freely admit to not keeping up with the field yet you devoutly support Davies and his work. He may or may not be onto something - but you cant support someone who is not providing a return on investment ie papers, data and collaboration. Hence why he spends more time outside of his lab looking for funding in places like China, Australia and Europe.
    Looks like Australia will be the new chronic sci research mecca.

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