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Pearse, et al. (2004). Combination Schwann cell, cAMP, and rolipram regenerates rat spinal cord

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    Pearse, et al. (2004). Combination Schwann cell, cAMP, and rolipram regenerates rat spinal cord

    Nature Medicine Online

    Damien D Pearse1, Francisco C Pereira2, Alexander E Marcillo1, Margaret L Bates1, Yerko A Berrocal1, Marie T Filbin3 & Mary Bartlett Bunge1, 4, 5

    Published online: 23 May 2004 | doi:10.1038/nm1056

    cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury

    1  The Miami Project to Cure Paralysis, University of Miami School of Medicine, 1095 NW 14th Terrace, Miami, Florida 33136, USA.

    2  Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 2415, Sao Paulo, CEP 05508-900, Brazil.

    3  Biology Department, Hunter College, 695 Park Ave., New York, New York, USA, 10021.

    4  Department of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, Florida 33136, USA.

    5  Department of Neurological Surgery, University of Miami School of Medicine, Miami, Florida 33136, USA.
    Correspondence should be addressed to Damien D Pearse dpearse@miamiproject.med.miami.edu

    Abstract: Central neurons regenerate axons if a permissive environment is provided; after spinal cord injury, however, inhibitory molecules are present that make the local environment nonpermissive. A promising new strategy for inducing neurons to overcome inhibitory signals is to activate cAMP signaling. Here we show thatcAMP levels fall in the rostral spinal cord, sensorimotor cortex and brainstem after spinal cord contusion. Inhibition of cAMP hydrolysis by the phosphodiesterase IV inhibitor rolipram prevents this decrease and when combined with Schwann cell grafts promotes significant supraspinal and proprioceptive axon sparing and myelination. Furthermore, combining rolipram with an injection of db-cAMP near the graft not only prevents the drop in cAMP levels but increases them above those in uninjured controls. This further enhances axonal sparing and myelination, promotes growth of serotonergic fibers into and beyond grafts, and significantly improves locomotion. These findings show that cAMP levels are key for protection, growth and myelination of injured CNS axons in vivo and recovery of function.

    #2
    Wise, I heard about this on the news last night, they said that they got 70% recovery in rats and that they could tell that the legs where functioning as a result of Brain response not muscular or other, can you put this in Lay-Mans terms for us to understand? It certainly is startling since I haven't heard anything for a while and the media seems to be hyping the find, or maybe its miami, but your thoughts on what this is and what it means would be appreciated.

    Comment


      #3
      xmarine,

      I believe this is one of the most significant studies published this year on spinal cord injury for the following reasons:

      1. It shows the importance of combining therapies, i.e. a cell transplant with another therapy that stimulates axons to grow despite the presence of growth inhibitors.

      2. This is functional regeneration, i.e. large numbers of axons growing across the injury site and making connections with neurons below the injury site and associated with significant motor recovery in the rat. By the way, I would not put so much credence in the 70% value. I don't think that the data indicates that the rats have recovered 70% of their function (they were really only testing some of the function and the BBB scores did not show a 70% improvement), nor do I think that they have regenerated 70% of the axons in the spinal cords that they have regenerated.

      3. This is a feasible therapy for clinical trial.

      Please note that there are several other combination therapies that will be published in the coming months. This is the first but by no means the only combination therapy that will be reported this year.

      Wise.

      Comment


        #4
        Originally posted by Wise Young:

        Please note that there are several other combination therapies that will be published in the coming months. This is the first but by no means the only combination therapy that will be reported this year.

        Wise.
        The important questions. [img]/forum/images/smilies/biggrin.gif[/img]

        1) Is this, in your opinion, the best combination therapy you know of that will be published?

        2) Is this the only combination therapy you are aware of that is currently feasible for clinical trials in the US?

        Thanks for all you do, Wise. [img]/forum/images/smilies/smile.gif[/img]

        -Steven
        ...i heard a little girl, and what she said was something beautiful, to give your love no matter what, is what she said
        ...it's worse than we thought. it turns out the people at the white house are not secret muslims, they're nerds.

        Comment


          #5
          Sorry this is tangential and maybe belongs elsewhere in your site, but -- any news yet on the results of the Phase II trial on rolipram for multiple sclerosis? ClinicalTrials.gov lists the study as Completed but contains no links to post-completion articles (it's probably early days still). http://www.clinicaltrials.gov/ct/sho...011375?order=1

          Comment

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