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  • Spinal Cord Injury Site "Scar Tissue"

    Originally Posted by Wise Young:

    As I have explained many times here and elsewhere, I disagree with the use of the word "scar" to describe what is happening at the spinal cord injury site. To me, scar means a fibrous collagenous tissue that is formed by fibroblasts (skin cells) to heal a cut in skin and other tissues. Normally, there are no fibroblasts in the spinal cord. Scar does form in the spinal cord when one uses a knife to cut the spinal cord and does not repair the dura afterward. The meninges do have fibroblasts but they usually do not invade into the spinal cord unless there has been a penetrating wound of the spinal cord. After contusion or compression injuries (which is what happens to a large majority of human spinal cords), there is no penetrating wound of the spinal cord and few or no fibroblasts in the spinal cord.

    I know that many scientists use the word scar in their descriptions of spinal cord injuries and have made it a primary target of their research. I disagree with this use of the word and have publicly criticized the suggestion that "scar" is the main obstacle to regeneration. I believe it is an artifact of their spinal cord injury model where they cut into the spinal cord and then fail to close the dura. I think that this is why Dr. Davies and almost every scientist who use the dorsal hemisection, lateral hemisection, or transection models of spinal cord injury emphasize scar formation . When fibroblasts invade into the spinal cord, astrocytes proliferate to wall them off (because they are foreign to the central nervous system and it is the job of astrocytes to segregate the central nervous system from surrounding tissues). When this happens, I agree that scar is forming in the spinal cord and poses a significant barrier to axonal growth.

    I have spent 30 years studying contusion injuries of the spinal cord. The vast majority of people with spinal cord injury have had contusions, compression, or ischemic lesions of the spinal cord. These types of injuries have little or no fibroblast invasion of the injury site. There is gliosis but these do not form physical barriers to axonal growth. In 1997, a group of 8 leading spinal cord injury centers in the United States (the Multicenter Animal Spinal Cord Injury Study) studied over 700 contused rat spinal cords (this is part of the multicenter animal spinal cord injury study). We found a majority (I believe >70%) of the contused spinal cords have a matrix of glial cells and Schwann cells at the injury center with many axons running through the middle of the injury site. Some of the spinal cords form cysts at the injury site. None had collagenous scars with fibroblasts.

    The continuous and repeated use of the word "scar" is unfortunate for several reasons. First, many people with spinal cord injury think that they are not regenerating because of a "scar" in their spinal cord. They and even some surgeons think that the answer to the scar is to cut it out. Second, in my opinion, investigators are targeting the wrong culprits. Glia are not enemies of regeneration. Glia are necessary to separate the central nervous system from the surrounding tissues. There are plenty of glia in our central nervous system and they are not the reasons why axons are not regenerating. Third, there are many obstacles to regeneration, including extracellular matrix proteins called chondroitin-6-sulfate-proteoglycans (CSPG) and myelin-based inhibitors such as Nogo that block axonal growth. Cysts can block axonal growth. There is a lack of prolonged growth factor stimulation needed to sustained long distance axons regeneration. "Scar" is seldom the main obstacle to regeneration.

    Please understand that I am not saying that research to assess ways to prevent or reverse "scar" in the spinal cord should not be done. If people use the word scar, I think that it should be clearly defined. Gliosis does not mean "scar". We should not be using these words interchangeably. Gliosis means an overgrowth of astrocytes. Scar is formed by fibroblasts and usually is found in skin but can occur in the spinal cord if it is cut and fibroblasts are allowed to invade into the spinal cord. I realize that people think that this is just semantics but unfortunately wrong words can lead to wrong actions.

    Wise.

    MASCIS Study on contusion injury in rats,
    • Beattie MS, Bresnahan JC, Komon J, Tovar CA, Van Meter M, Anderson DK, Faden AI, Hsu CY, Noble LJ, Salzman S and Young W (1997). Endogenous repair after spinal cord contusion injuries in the rat. Exp Neurol 148: 453-63. Department of Cell Biology, Ohio State University College of Medicine, 333 West 10th Avenue, Columbus, Ohio 43210, USA. Contusion injuries of the rat thoracic spinal cord were made using a standardized device developed for the Multicenter Animal Spinal Cord Injury Study (MASCIS). Lesions of different severity were studied for signs of endogenous repair at times up to 6 weeks following injury. Contusion injuries produced a typical picture of secondary damage resulting in the destruction of the cord center and the chronic sparing of a peripheral rim of fibers which varied in amount depending upon the injury magnitude. It was noted that the cavities often developed a dense cellular matrix that became partially filled with nerve fibers and associated Schwann cells. The amount of fiber and Schwann cell ingrowth was inversely related to the severity of injury and amount of peripheral fiber sparing. The source of the ingrowing fibers was not determined, but many of them clearly originated in the dorsal roots. In addition to signs of regeneration, we noted evidence for the proliferation of cells located in the ependymal zone surrounding the central canal at early times following contusion injuries. These cells may contribute to the development of cellular trabeculae that provide a scaffolding within the lesion cavity that provides the substrates for cellular infiltration and regeneration of axons. Together, these observations suggest that the endogenous reparative response to spinal contusion injury is substantial. Understanding the regulation and restrictions on the repair processes might lead to better ways in which to encourage spontaneous recovery after CNS injury.

  • #2
    thanks for posting this

    It's what I suspected. Now I won't need to reorder copper peptide serum that I was putting on my neck scar. I read that it increases decorin naturally which is antifibrotic.

    Jan

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    • #3
      Does anybody know if the "scar tissue" that Dr. Lima removes from patients has been examined to determin if it is gliosis, fibrous collagenous tissue or both??
      In God we trust; all others bring data. - Edwards Deming

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      • #4
        How much of this reasoning applies to people who had surgery to repair or stabilize disks in their necks or spine? Does such surgery often cut into the dura?

        Forgive me that i am not knowledgeable about my own surgery but I was not feeling well at the time.

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        • #5
          Thank you for this medical insight. I have spend time trying to imagine a spinal cord scar, particularly as my injury did not involve physical disruption of the cord. Might be a good idea to deprecate this term.
          2010 SCINet Clinical Trial Support Squad Member
          Please join me and donate a dollar a day at http://justadollarplease.org and copy and paste this message to the bottom of your signature.

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          • #6
            marked.

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            • #7
              topic scarring from spinal cord injuries or diseases.

              This topic comes up from time to time and is critical to our discussions on stem cell development for cures. The Geron tiral is for acutes who have been injured within 14 days to avoid scarring issues. Many of our posts discuss scarring as a potential problem to get nerve regrowth and potential cures. My understanding is that Wise sees this as a misnomer and thinks his therapies can alleviate this condition. I spoke with JohnsHopkins medical personel who are working with Geron on their trial and see scarring as an issue. Han Kiersted of UCSD sees scarring as an issue also. We all need to be aware of this issue for chronics and discuss this issue for our path forward. Wise's trial is for chronics which we are all classifed as. Perhaps Wise will discuss this at length again and we all can join in. This will be critical for our benefitting from any therpies that might come through.

              keeping on

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              • #8
                This is certainly a subject I think about a lot. In the first post on this thread, Dr. Young's views on use of the word "scar" in relation to SCI are set forth. What I take from the post, is that different types of tissue formation and cell moblization accompany specific kinds of injuries, and not all thickening is actually scar.

                If I understand the post correctly, the central issue is whether or not thickening results from an influx of fibroblasts or glial cells - and Dr. Young also says that some true scar formation is likely an artifact of research methods. The variations between acute/chronic and traumatic/disease-related injuries must make for an extraordinarily complicated picture, even on a case-by-case basis - especially since many of us have features of several types of injury. Very perplexing.
                MS with cervical and thoracic cord lesions

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                • #9
                  Thanks for posting the link Bonnette. These are also good explanations.
                  https://www.carecure.net/forum/showp...51&postcount=3

                  https://www.carecure.net/forum/showp...77&postcount=3

                  Dr. Young has done a great job explaining the scar issue in lots of different posts for us. These are ones I like the best.
                  Last edited by GRAMMY; 05-13-2011, 05:43 PM.
                  http://spinalcordresearchandadvocacy.wordpress.com/

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                  • #10
                    A group in Minnesota; might be spinal cord society, is working on scarring. I think they may be considering;FES scar abalation, and stem cell. I've seen and read many of the researchers that say this is a problem. Wise's explanation is more thourogh and he seems to have a good explanation and possible solutions to whatever we may call it; scarring or thckening. Bottom line , it must be addressed to allow benficail therpies for chronics.

                    keeping on

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                    • #11
                      They certainly are! Thanks, GRAMMY.
                      MS with cervical and thoracic cord lesions

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                      • #12
                        From what I was told and looking at my last MRI, my cord wasn't severed leaving me an incomplete C5/6. The MRI makes my cord look like an hour-glass. Leading me to believe that if the surrounding tissue, whatever it may be, was removed, that it may allow regneration of cord cells. It just seems to me that "clearing the path" may allow regeneration. mark

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                        • #13
                          Originally posted by 4tun8 View Post
                          From what I was told and looking at my last MRI, my cord wasn't severed leaving me an incomplete C5/6. The MRI makes my cord look like an hour-glass. Leading me to believe that if the surrounding tissue, whatever it may be, was removed, that it may allow regneration of cord cells. It just seems to me that "clearing the path" may allow regeneration. mark
                          4tun8, what you are suggesting is precisely what I believe should not be done. There is *no* evidence that removing "scar" improves regeneration. Many studies have tried to remove scar and, to my knowledged, none have resulted in regeneration of the spinal cord.

                          Chondroitin-6-sulfate proteoglycan (CSPG) is an extracellular matrix material. This material is made by glial cells when they try to wall off what they believe is peripheral tissues from the spinal cord (and brain). CSPG will stop axonal growth but CSPG is not "scar". It is just extracellular material.

                          A bacterial enzyme called chondroitinase ABC will break down CSPG. Over 100 papers have been published showing that chondroitinase will break down CSPG and allow axons to grow in the spinal cord and the central nervous system.

                          Physical removal of the spinal cord produces scar. To cut a piece of the spinal cord out is to allow fibroblasts into the spinal cord. To put a piece of nasal mucosa into the spinal cord is to put fibroblasts into the spinal cord. It creates more gliosis and true scar where there may not have been before.

                          Nobody has ever removed a piece of the spinal cord without more gliosis forming in the surrounding cord. This concept of removing a piece of the spinal cord in ord