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Thread: Finding the right connection after spinal cord injury

  1. #1

    Smile Finding the right connection after spinal cord injury

    Public release date: 2-Aug-2009
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    Contact: Debra Kain
    ddkain@ucsd.edu
    619-543-6163
    University of California - San Diego

    Finding the right connection after spinal cord injury




    IMAGE: This image shows a target cell in the brain (green) contacted by an axon (red) regenerating into the brain from the spinal cord.
    Click here for more information.

    In a major step in spinal cord injury research, scientists at the University of California, San Diego School of Medicine have demonstrated that regenerating axons can be guided to their correct targets and re-form connections after spinal cord injury. Their findings will be published in the advance online edition of the journal Nature Neuroscience on August 2.
    In the last few years, researchers have shown that the severed wires of the spinal cord, called axons, can be induced to regenerate into and beyond sites of experimental spinal cord injury. But a key question has been how these regenerating axons, on reaching the end of an injury site, can be guided to a correct cell target when faced with millions of potential targets. Further, can regenerating axons form functional, electrical connections called synapses?
    "The ability to guide regenerating axons to a correct target after spinal cord injury has always been a point of crucial importance in contemplating translation of regeneration therapies to humans," said senior author Mark Tuszynski, MD, PhD, professor of neurosciences and director of the Center for Neural Repair at UC San Diego, and neurologist at the Veterans Affairs San Diego Health System. "While our findings are very encouraging in this respect, they also highlight the complexity of restoring function in the injured spinal cord."
    The UC San Diego study looked at regenerating sensory axons in rat models of spinal cord injury. Sensory systems of the body send axons – long, slender projections of the neuron – into the spinal cord to convey information regarding touch, position, and pain. Many sensory axons are covered by an insulating myelin sheath which helps these impulses travel efficiently to the brain.
    In certain spinal cord injuries, the axons are severed and the myelin sheath damaged. Loss of these systems results in an inability to feel or sense the body. The axons can no longer link to their targets in the brain, which blocks the electrical impulses from reaching the central nervous system.
    The UC San Diego scientists showed that regenerating axons can be guided to correct targets using a type of chemical hormone called a growth factor. The team utilized a type of chemical hormone, a nervous system growth factor called neurotrophin-3 (NT-3), to guide regenerating sensory axons to the appropriate target and support synapse formation. Regeneration required two other treatments at the same time: placing a cell bridge in the spinal cord injury site to support axon growth, and a "conditioning" stimulus to the injured neuron that turned on regeneration genes for new growth.
    When the growth factor was placed in the correct target as a guidance cue, axons regenerated into it and formed synapses. When the growth factor was placed in the wrong target, axons also followed the growth factor and grew into the wrong region.
    Using high-resolution imaging systems, the scientists showed that regenerating axons guided to the correct cell formed synapses that were precisely on target. These axons contained rounded vesicles – small packets at the end of the axon, packed with the chemical messengers needed to support electrical activity in the newly formed circuit.
    Nonetheless, the connections were not electrically active. Additional study revealed the likely reason for this: the regenerating axons were not covered in myelin, the insulating material of the nervous system.
    "Restoring axonal circuitry is complex, requiring several concurrent therapies to achieve axonal regeneration into and beyond a spinal cord lesion site," said Tuszynski. "But, just as an electrical circuit needs insulation so it doesn't short-circuit, it appears that these regenerating axons require restoration of the myelin sheath to ultimately restore function." This will be the next step in the team's research.
    In earlier research (reported in PNAS April 6), the UC San Diego team achieved the first corticospinal motor axon regeneration by genetically engineering injured neurons to over-express receptors for another type of nervous system growth factor called brain-derived neurotrophic factor (BDNF). The growth factor was delivered to a brain lesion site in injured rats, where axons responded and regenerated into the injury site.

    ###

    The lead author of the Nature Neuroscience study is Laura Taylor Alto of UCSD's Department of Neurosciences. Additional contributors include Leif A. Havton of UCLA, and James M. Conner, Edmund R. Hollis II and Armin Blesch of UCSD Department of Neurosciences. Their work was supported by the National Institutes of Health, the Veterans Administration, the International Spinal Research Trust, Wings for Life, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and the Bernard and Anne Spitzer Charitable Trust.


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  2. #2
    Thanks for the post!

    This is some of the best news I've read in years.
    Always been my biggest fear about regenerative therapies,
    getting the connections to be the right ones...

  3. #3

    Chemical hormone that can help find right connection after spinal cord injury

    A scientific team at the University of California, San Diego School of Medicine have recently shown that it is possible to guide regenerating axons—severed wires of the spinal cord—to their correct targets and re-form connections after spinal cord injury.

    You may read more here:
    http://www.askmenhealth.org/blog/

  4. #4
    Senior Member Schmeky's Avatar
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    This is excellent news . . . . . but, there is no mention of overcoming an inhibitory environment (chronics).

    I have to assume Tuszynski knows Hans Kierstad has already addressed the remyelination issue. So is Tuszynski going to now try to figure out what seems to have already been figured out?

  5. #5
    Senior Member DA's Avatar
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    i thought L1 guidance already did this.

  6. #6
    This research sounds great! So now what? How does it get out of the lab?
    please . . .test what you already know; and give us what you have. we may not be dying, but we certainly are not living either

  7. #7
    Quote Originally Posted by Nicksdad View Post
    This research sounds great! So now what? How does it get out of the lab?
    A few million to start? Money = cure

  8. #8
    Senior Member redbandit's Avatar
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    Quote Originally Posted by Schmeky View Post
    I have to assume Tuszynski knows Hans Kierstad has already addressed the remyelination issue.
    Maybe we shouldn't assume, the statement in the article concerning myelin was:
    "This will be the next step in the team's research".

    I'd hate to see him re-invent the wheel, maybe someone should forward Kiersted's results to him.

    The results are both encouraging and discouraging. Like the article said, the axons created appropriate synapses when the NT-3 was placed in the correct target region, however no electrical impulse was seen. So the list for an effective combination therapy for chronics grows longer and more complicated still.

    But, maybe the good news is that all the pieces may be starting to fall into place - so to speak. A collaborative effort between Drs. Stephen Davies, Hans Kierstad, and Mark Tuszynski might yield a promising therapy. GDPs could be used for nerve grafts, decorin to assist the newly sprouting axons through the scar, NT-3 would guide the emerging axons to the appropriate targets, and Kierstad's treatment would remyelinate the completed circuit. Even if that's feasible though, completing clinical trials for a therapy that complex would take a LOT of time. Each component would have to be tested sequentially, then cumulatively; animals first, humans next. The good news is that a lot of the animal testing for each individual therapy has been done, and Davies is currently working on decorin(I think) and GDPs in chronic rats. I'm not sure where the other labs are with their testing. I would be interested in hearing Wise's take on it. I'm just writing stream of consciousness right now, probably a total pipe dream.
    Last edited by redbandit; 08-04-2009 at 08:25 PM.

  9. #9
    You know, they might get this SCI cure thing figured out in another 50 years or so...

  10. #10
    Senior Member Schmeky's Avatar
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    Quote Originally Posted by Redbandit
    A collaborative effort between Drs. Stephen Davies, Hans Kierstad, and Mark Tuszynski might yield a promising therapy.
    I agree, but with all due respect, you would have better luck mixing oil, water, and tarter sauce. Never ever gonna happen. It's a shame to.

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