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Thread: cAMP Levels & Recovery?

  1. #11
    Chris, sorry to contradict you but the data from Dr. Huang suggest conclusions other than the ones that you have come to. First, over 70% of the patients that Dr. Huang treated were ASIA A (complete). They also showed recovery. Second, about half of the patients have thoracic spinal cord injuries and they also showed about the same degree (albeit modest) sensory and motor improvement. Third, remyelination takes time. In rats, for example, we find that it takes a minimum of 3 weeks for any remyelination to take place and sometimes 4-6 weeks. In the trials, most of the patients were showing some improvement within the first 3 weeks. Wise.

    [This message was edited by Wise Young on 05-02-04 at 08:48 PM.]

  2. #12
    Oh well, I gave it a shot.

    Theories are theories

  3. #13
    Dr. Young, I found the following extract
    Dibutyryl-cAMP (dbcAMP) up-regulates astrocytic chloride-dependent l-[3H]glutamate transport and expression of both system xc subunits which contain the following

    "Effective clearance of glutamate, a major excitatory amino acid in the mammalian CNS, from the synaptic cleft is necessary to maintain efficient synaptic transmission. "

    Most of the abstract is way too complicated for me to understand, but could the conclusion above be one of the reasons that some the therapies are seeing immediate effects. If astrocytes started clearing glutamate at the injury site, would this allow existing axons which may not have been working to start transmitting again, simply because the "noise" from the glutamate inhibited their transmission?

  4. #14
    Carl R,

    Marie Filbin showed the elevating cAMP in axons allows them to ignore all the growth inhibitors in the spinal cord, including Nogo, CSPG, and MAG. This alone is sufficient to explain the effects of cAMP and rolipram on axonal regeneration. There of course may be other effects of the treatment.

    Wise.

  5. #15
    Senior Member kilgore's Avatar
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    While there's evidence that increasing cAMP aides regeneration like:
    Neumann S, Bradke F, Tessier-Lavigne M and Basbaum AI (2002)

    "Here we show that microinjection of a membrane-permeable analog of cAMP ... injured axons regrow into the spinal cord lesion, often traversing the injury site."


    But here's an old Acordia rat study that shows no benefit from rolipram in rats:

    http://www.acorda.com/old/sfn.htmg

    "In this study, rolipram did not demonstrate any beneficial effects on neurological
    outcome following SCI in adult rats."


    Does this mean that it's pointless to take rolipram by itself? It seems like it should be helpful since it does increase cAMP levels.

  6. #16
    kilgore,

    What Mary Bunge found in their study was that taking rolipram alone did not raise cAMP. You have to understand what rolipram does. It prevents breakdown of cAMP but, by itself, it does not increase cAMP to sufficient levels. However, when they injected dibutyryl cAMP (a form of cAMP that gets across cell membranes) into the spinal cord at the time of Schwann cell transplants and treated with rolipram for 2 weeks, they got a rise of cAMP in the spinal cord that was sustained for 2 weeks. This was then associated with very significant regeneration.

    Wise.

  7. #17
    Dr. Young, a couple more questions regarding dibutyryl cAMP. Can you speculate on what the dosage might be in humans as compared to what they used in mice? EMD Biosciences has dibutyryl cAMP listed as $237 for 100 mg. I am trying to get an idea of how expensive the drug would be for trials. Also, does anyone have the rights to dibutyryl cAMP? In other words, is there any incentive for a company to invest in the product and Profit from its use?

    Lastly, am I correct in assuming that since I have been on Theophylin for over two years that I would not need Rolipram since they are both pd4 inhibitors?

  8. #18
    Dr. Young, any luck with your Forskolin studies? Here's a list of natural sources for cyclic AMP, don't know if ingesting it would decrease its potency or if an increase in serum cAMP would stimulate cns regeneration in chronic injuries but just thought it was interesting that many plants are reported to possess the ability to significantly increase cAMP levels in humans.

    Coleus Forskohlii is one of the world's most researched plants. The majority of research has focused on forskolin, which is believed to be the plant's most active constituent. It is known to activate the enzyme adenylate cylclase that forms cyclic AMP within cells. Forskolin is shown to exert a 6- to 400-fold increase in levels of cAMP.

    Bupleurum root has also been shown to increase cAMP.

    Feverfew herb is known to stimulate the formation of cyclic AMP.

    In addition to cyclic AMP stimulating activity, Chinese Skullcap root possesses antioxidant activity.

    Jujube dates are reported to stimulate cAMP and support liver, nervous system and respiratory health.

  9. #19
    Senior Member kilgore's Avatar
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    I tried Coleus Forskohlii a few years ago. Back in the Spinewire days, someone posted that snorting the powder from the capsules gave a quick temporary effect similar to that of 4-AP. I had tried 4-AP, but found that it only made me dizzy, so I wasn't optimistic about the Forskohlii, but it was worth a shot.
    Snorting the stuff was supposed to bring the chemicals through the blood/brain barrier. It was like inhaling a mixture of nutmeg and dirt. I only tried it a few times and felt nothing significant, except for the desire to blow my nose. Since I had a full bottle, I took the rest orally (once a day) for the rest of the month. I didn't notice any changes.

  10. #20
    Carl R,

    Cyclic AMP (cAMP) is *the* universal intracellular messenger. Discovered nearly four decades ago by Earl Sutherland who was awarded the Nobel prize for the work, it is made by cells and is the signal for many cellular functions, including growth. It is made by an enzyme called adbroken down by phosphodiesterase 4 (the phosphodiesterase that is specific for the central nervous system).

    Dibutyryl cAMP is simply a form of cAMP that crosses membranes. There are many other forms http://www.biolog.de/othercak.html that may work equally as well. Rolipram is a phospodiesterase-4 (PDE4) inhibitor and there are many of those as well. The main problem with rolipram is is pro-emetic effect (vomiting).

    Wise.

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