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

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

    This is indeed good news for us chronics.

    Comment


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

      Comment


        #4
        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

        Comment


          #5
          I will stay with the wise one... that's a positive thing for me today.
          keiffer66

          Comment


            #6
            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.

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              #7
              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; 9 Oct 2006, 6:45 AM.

              Comment


                #8
                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; 9 Oct 2006, 10:53 AM.
                My mouth is like a magician's hat, never know what might come out of it.

                Comment


                  #9
                  macska ,
                  hi, i am sorry about your son, i hope he is doing ok. mine is t3-4 asia A and it seems that bullet never touched the cord (soft tissue) , but the impact ,and the force and velocity of the bullet on the bone caused disruption of spinal cord.
                  take care,and stay positive as much as you can,
                  all the best
                  Last edited by kz; 9 Oct 2006, 11:20 AM.

                  Comment


                    #10
                    Thanks KZ,

                    We are positive, and he is doing good, but we are also being realistic. He is 4 years post.
                    My mouth is like a magician's hat, never know what might come out of it.

                    Comment


                      #11
                      Wise. Wouldn’t neurosurgery to the cord result in a fibroblast invasion as well when the surgeon’s knife cut trough the dura and so on into the cord itselfe? Right?

                      Comment


                        #12
                        The way I dumb this down (as DA would say) for my thinking process is using something I have seen.

                        You have a serious bruise on your skin and it heals and leaves no scar. You have a tiny cut and after it heals you have a scar.

                        Doesn't mean though that when you were bruised you didn't injure alot of surrounding tissue..you most certainly did..but you didn't disconnect the skin thus it doesn't have to form scar tissue to reconnect the two ends of the skin.

                        Just my simply minded way of trying to understand.
                        Life isn't about getting thru the storm but learning to dance in the rain.

                        Comment


                          #13
                          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.

                          Comment


                            #14
                            Originally posted by Leif
                            Wise. Wouldn’t neurosurgery to the cord result in a fibroblast invasion as well when the surgeon’s knife cut trough the dura and so on into the cord itselfe? Right?
                            This is true. It is the reason many doctors are reluctant to cut into the spinal cord unless they have to (like in the case of a spinal cord tumor). It is one of the reasons why I have been uncomfortable with the surgery being carried out in Portugal where they cut out a part of the spinal cord that supposedly has the "scar". Several animal studies have suggested that if the dura is carefully closed after the injury and prevented from adhering to the spinal cord, fibroblast invasion in to the injury site is limited. In the ChinaSCINet, we are planning to introduce the cells through a small puncture as opposed to cutting into spinal cord.

                            I have now studied contused spinal cords of animals for over 20 years. In general, contused spinal cords do not show thick deposits of collagen inside the spinal cord at the injury site. Collagen is made by fibroblasts. While there may be some collagen deposits on the surface of contused spinal cord, especially where there is adhesion between the spinal cord and arachnoid, these are usually limited to the surface. By the way, the spinal cord contain extracellular matrix molecules that prevent migration of cells that the spinal cord considers to be "peripheral". For example, generally fibroblasts and Schwann cells (which the spinal cord treats as peripheral cells) injected into the spinal cord will not migrate far from the injection site into the surrounding cord.

                            For many years, the Schwab group in Switzerland used the so-called "over-hemisection" model to examine regeneration. However, a number of years ago, they adopted our contusion model. I found the Tuzynski paper particularly interesting because they cut into the spinal cord and find that the resultant "scar" does not seem to impede axonal growth in the cervical spinal cord.

                            Wise.

                            Comment


                              #15
                              I wonder if other scientists, or researchers, pay as much attention to your research
                              as you do to with theirs?

                              Comment

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