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Thread: Study of the effects of "chronic scar" on axonal growth in spinal cord injury

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  1. #1

    Study of the effects of "chronic scar" on axonal growth in spinal cord injury

    One of the most frequently asked questions on this site is what should be done (if anything) about the "scar" at the injury site. I have always answered that the "scar" at the injury site is different from what we would normally consider a scar on the skin or other tissues, that it is not a fibrous scar but one that is composed of mostly astrocytes or glial cells. Some scientists call this a "glial scar" but I objected to such terminology because, as a former surgeon, I think of scar as being produced by fibroblasts and involve collagen. In any case, this very interesting study from the Tuszynski laboratory suggests that glial scars do not produce inpenetrable barriers to axonal growth. They transplanted bone marrow stromal cells in the cervical spinal cord of rats and then examined axonal growth through the "scar". Despite extensive astrocytosis around the lesgion site with dense deposition of the inhibitory extracellular matrix molecule NG2 (a form of chondroitin-6-sulfate-proteoglycan), they found that axons grew through the lesion site, particularly when they stimulated the growth with NT-3 (which by the way is something that lithium seems to stimulate the production of in umbilical cord blood). They authors conclude that the "chronic scar" does not create inpenetrable barriers to axonal growth.

    [*] Lu P, Jones LL and Tuszynski MH (2006). Axon regeneration through scars and into sites of chronic spinal cord injury. Exp Neurol Cellular and extracellular inhibitors are thought to restrict axon growth after chronic spinal cord injury (SCI), confronting the axon with a combination of chronic astrocytosis and extracellular matrix-associated inhibitors that collectively constitute the chronic "scar." To examine whether the chronically injured environment is strongly inhibitory to axonal regeneration, we grafted permissive autologous bone marrow stromal cells (MSCs) into mid-cervical SCI sites of adult rats, 6 weeks post-injury without resection of the "chronic scar." Additional subjects received MSCs genetically modified to express neurotrophin-3 (NT-3), providing a further local stimulus to axon growth. Anatomical analysis 3 months post-injury revealed extensive astrocytosis surrounding the lesion site, together with dense deposition of the inhibitory extracellular matrix molecule NG2. Despite this inhibitory environment, axons penetrated the lesion site through the chronic scar. Robust axonal regeneration occurred into chronic lesion cavities expressing NT-3. Notably, chronically regenerating axons preferentially associated with Schwann cell surfaces expressing both inhibitory NG2 substrates and the permissive substrates L1 and NCAM in the lesion site. Collectively, these findings indicate that inhibitory factors deposited at sites of chronic SCI do not create impenetrable boundaries and that inhibition can be balanced by local and diffusible signals to generate robust axonal growth even without resecting chronic scar tissue. Department of Neurosciences-0626, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Veterans Affairs Medical Center, San Diego, CA 92161, USA. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=17014846

  2. #2
    --They authors conclude that the "chronic scar" does not create inpenetrable barriers to axonal growth.

    This is indeed good news for us chronics.

  3. #3
    Latest review by Schwab et al. does mention fibroblasts and scar as a barrier. Progress in Neurobiology 78 (2006) 91-116.

  4. #4
    Senior Member Norm's Avatar
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    Can't everyone doing research get on the same page?
    "Some people say that, the longer you go the better it gets the more you get used to it, I'm actually finding the opposite is true."

    -Christopher Reeve on his Paralysis

  5. #5
    Quote Originally Posted by Cripply
    Latest review by Schwab et al. does mention fibroblasts and scar as a barrier. Progress in Neurobiology 78 (2006) 91-116.
    Cripply, if you use a knife and cut the spinal cord, there is fibroblast invasion and a fibrous scar does occur. However, if you contuse the spinal cord, only glial proliferation occurs at the edges of the lesion site. Penetrating wounds of the spinal cord can cause fibrous scars. Contusions do not. Most people have contusions.

    Wise.

  6. #6
    dr. young,
    hi, how about gunshot wound that caused "complete" asia A paralyis,when the bullet hit the bone and did not even hit the spinal cord (soft tissue) ? what is the main reason of "complete" asia paralysis when the bullet hit the spine (bone) and it did not even hit the soft tissue ? what kind of scar exist in this kind of situation ?what is the main reason of "complete" asia A paralysis in this kind of situation (this is my situation)? what is causing the disruption of spinal cord in this kind of situation ? is this kind of injury harder to cure or easier compare to contusion ,or it does not matter at all when it comes to any kind of treatment (cure) ? please explain this kind of injury a little more.
    thanks so much
    Last edited by kz; 10-09-2006 at 06:45 AM.

  7. #7
    KZ

    The extreme heat from the projectal also causes a lot of damage to the spinal cord, even if it did not touches the cord it self. That is why you are classified Asia A. The cord has most likely sustained damage from the heat.

    In my son Jordans' case the bullet travelled through the vertebrea and cut his cord at the T4 level completely. I am pretty sure that there is signifficant scarring and from looking at his CT scans the bone is also very damaged even to date. He had a commuted fracture and there is still a lot of debree in the spinal canal and surrounding area.
    Often wonder how can be ever fixed.

    Dr. Young, just to clarify, than is cases like Jordan the scarring would be classified as fibrous? To be honest I believe that his type of injury is pretty much the worst case scenario.
    Last edited by macska; 10-09-2006 at 10:53 AM.

  8. #8
    Quote Originally Posted by kz
    dr. young,
    hi, how about gunshot wound that caused "complete" asia A paralyis,when the bullet hit the bone and did not even hit the spinal cord (soft tissue) ? what is the main reason of "complete" asia paralysis when the bullet hit the spine (bone) and it did not even hit the soft tissue ? what kind of scar exist in this kind of situation ?what is the main reason of "complete" asia A paralysis in this kind of situation (this is my situation)? what is causing the disruption of spinal cord in this kind of situation ? is this kind of injury harder to cure or easier compare to contusion ,or it does not matter at all when it comes to any kind of treatment (cure) ? please explain this kind of injury a little more.
    thanks so much
    Tissue and cell parts are elastic. If you stretched them slowly, they can stretch quite a lot perhaps 2-3x. However, if you stretch them too far or too fast, they break. Axons are a lot like rubber bands. The critical breaking velocity for them is about 0.5 meters/second.

    A contusion of the spinal cord with a weight that is dropped from 12.5-75.0 mm height compresses the spinal cord at the rate of 0.4-1.2 meters/sec. Because the spinal cord is really like a tube of jello, the only directions that the spinal cord can go when it is compressed is longitudinal.

    Paradoxically, myelinated axons are the first and most sensitive to stretch. The reason is that most of the axon is covered with myelin except for areas between the myelin, called nodes of Ranvier. Since the parts of axons that are covered with myelin do not stretch as much, all the stretch is concentrated on the nodes of Ranvier.

    The gray matter of the spinal cord, however, is damaged due to shearing forces that occur with the spinal cord is indented. Also, the shearing forces can damage blood vessels that cause bleeding into the spinal cord. Blood is toxic to the tissue and contributes to the damage.

    Now, a bullet can damage the spinal cord without penetrating into the spinal cord. In addition to possibly causing bone to indent the spinal cord, a bullet can also produce a shock wave that transmits through the spinal cord. The damage produced by the bullet depends on the velocity of the shock wave.

    While such "shock" waves have long been blamed for gunshot wounds, please note that many studies have suggested that these shock waves have been overestimated. Due to public protest, the U.S. government has stopped experiments involving gunshot wounds of the spinal cord in animals. However, studies carried out in China suggest that the bullet can pass close to the spinal column but will not damage the spinal cord unless the bullet contacts the spinal column bone.

    Wise.

  9. #9
    Quote Originally Posted by Wise Young
    Cripply, if you use a knife and cut the spinal cord, there is fibroblast invasion and a fibrous scar does occur. However, if you contuse the spinal cord, only glial proliferation occurs at the edges of the lesion site. Penetrating wounds of the spinal cord can cause fibrous scars. Contusions do not. Most people have contusions.

    Wise.
    My concern is that there might be differences between animals and humans in this regard. The paper does not say that the scar pictured is from a cut cord.

  10. #10
    Quote Originally Posted by Wise Young
    Cripply, if you use a knife and cut the spinal cord, there is fibroblast invasion and a fibrous scar does occur. However, if you contuse the spinal cord, only glial proliferation occurs at the edges of the lesion site. Penetrating wounds of the spinal cord can cause fibrous scars. Contusions do not. Most people have contusions.

    Wise.
    Wise,

    So basically I have a fibrous scar that is tethering my cord causing some of my pain. Is that correct?

    Pam

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