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Thread: What is the importance and are there treatments for scar tissues

  1. #1

    What is the importance and are there treatments for scar tissues

    A member asked this question in Private Topics. I thought that others may have the same question and will try to answer it in the Cure Forum.

    Just a quick question, can wise please tell me if there is any treatment for scar tissue as I have read a lot about it, and believe this stops recovery. Thank you for your time.
    The theory that scar tissue stops repair and regeneration of the spinal cord has been around for a long time. After many years of spinal cord injury research, I am very skeptical of this theory. Let me explain the different kinds of scar tissue that can form in the spinal cord, what they may do, and what treatments are available.

    When the spinal cord is injured, many cells at the injury site die, including cells that line the blood vessel and the spinal cord. This allows outside cells (particularly inflammatory white blood cells such as leukocytes, lymphocytes, and macrophages, as well as Schwann cells from the surround spinal roots) to invade the injury site. This is particularly true if there has been a wound of the spinal cord, such as occurs when a knife is used to cut the spinal cord or a bullet penetrates into the spinal cord.

    The spinal cord (and other parts of the central nervous system) recognize these cells as coming from outside the central nervous system (CNS). Cells in the spinal cord called astrocytes (also sometimes called glial cells) will proliferate (make more cells) that surround invading cells that are considered to be outside of the CNS. Astrocytic proliferation is sometimes called a "glial scar" because they are so think that they look a little like a scar in the spinal cord. Also, many researchers have noticed that axons (nerve fibers) don't like to grow through astrocytic scars.

    Glial scars are very different from the fibrous scars that form in other parts of the body. If you cut yourself, you will form a fibrous scar that has collagen in it. Such scars are made by fibroblasts or skin cells. These cells not only secrete collagen but also a class of proteins called chondroitin-6-sulfate-proteoglycan (CSPG) that is known to stop axonal growth.

    In addition, there is scarring that develops between the spinal cord and surrounding tissues. Due to the inflammation in the spinal cord and fibroblast invasion into the lining (arachnoid) of the spinal cord, the spinal cord form "adhesive" scars with surrounding tissues. Normally, the spinal cord slips and slides in the membranes but the presence of adhesive scars, particularly at the spinal roots, cause "tethering" of the spinal cord.

    In Portugal, Carlos Lima and his colleagues believe that scarring is an important barrier to axonal regeneration at the injury site. They consequently remove part of the spinal cord, presumably containing the "scar" at the injury site before they transplant part of the nasal mucosa into the spinal cord. I am not in favor of this for several reasons. First, most people still have some axons that cross the injury site. It is not clear that cutting a piece of the spinal cord injury site will not damage existing axons. Second, the surgery itself will introduce more astrocytic and possibly fibrous scarring in the spinal cord. The more damage that is done to the spinal cord by the surgery, the more likely there will be scar at the injury site. Third, blood and inflammation stimulates astrogliosis and adhesive scarring. If there is any hemorrhage from the surgery site, it may contribute to the formatin of arachnoiditis or an inflammation of the arachnoid membranes that hold cerebrospinal fluid (CSF).

    So, what can be done if one has scarring inside the spinal cord? It does not make sense to try to cut out scar surgically, if any, in the spinal cord for the following reasons. In addition to removing scar, one will may remove some remaining axons. Even though somebody may not have feeling or motor control below the injury level, this does not mean that there are no axons that cross the injury site. So-called "complete" spinal cord injuries are not necessarily complete. Many animal and human studies have suggested that somewhere around 10% of the axons in the spinal cord are necessary and sufficient for some function below the injury site. Therefore, even if you have no apparent function below the injury site, you may have some axons remaining. Surgery of the spinal cord may not only damage what is already there but may cause further scarring to occur.

    One possible approach to getting around or reducing the obstructive effects of "scar" inside the spinal cord (if you have any, I keep emphasizing this because I am not convinced that a majority of people have fibrous scar tissues in their spinal cord injury site) is to inject enzyme that breaks down chondroitin-6-sulfate-proteoglycan (CSPG). CSPG is deposited around the edges of the injury site by proliferating astrocytes and will stop axonal growth. An enzyme called chondroitinase (Chase) will break down CSPG and several laboratories have reported that Chase will promote regeneration in the spinal cord and other parts of the central nervous system. Several laboratories have been developing drugs or antibodies that prevent scar formation by blocking or preventing certain components of fibrous scarring.

    The adhesive scar that develops between the spinal cord and surrounding tissues is a much more common problem. Adhesive scarring of the lining of the spinal cord (called arachnoid) is a frequent complication of inflammation of the arachnoid, called arachnoiditis. Many people develop arachnoiditis as an aftermath of injury, infection, or hemorrhage (bleeding) of the spinal cord. Arachnoiditis can produce several serious problems. The first is tethering of the spinal cord. The spinal cord normally slips and slides within the arachnoid and dura. When it is tethered, any movement of the spinal cord will cause pulling and stretching of the spinal cord or its roots, contributing to damage of the cord. The second is blockade of cerebrospinal fluid (CSF) flow around the spinal cord. Normally, as much as a liter of CSF flow down the spinal cord in the subarachnoid space (the space between the arachnoid and the spinal cord). When this space is obstructed and CSF does not flow in the subarachnoid space, some of the flow may be diverted into the central canal. The central canal is normally a thin channel that is present in the middle of the spinal cord. When flow is increased in the central canal, the central canal may enlarge. Such enlargements are called syringomyelic cysts or syrinxes for short. Expansion of syrinxes may extend up and down the spinal cord from the injury site and may compress the cord. Both tethering and syrinxes may contribute to progressive neurological loss and pain.

    At the present, the only way of treating tethering of the spinal cord is surgery to expose the spinal cord and meticulously removing any adhesive scars between the spinal cord and arachnoid and dura. Please note that such "scars" are often very thin and delicate cobwebs. The surgery is often done under the microscope and is time-consuming. Many surgeons are reluctant to expose the injured spinal cord because the surgery itself may cause some damage to the cord and lead to more adhesive scarring.

    In the 1990's, there was a drug called Adcon gel that prevented such scarring. When placed on the spinal cord or the surrounding tissues, it prevents scarring. It is actually quite effective in preventing scarring but it also prevents healing of the dura (the membrane that surrounds the arachnoid). In the late 1990's, several patients developed CSF leaks as a result of Adcon gel and the drug was withdrawn from the market for further safety testing. The company that made Adcon gel went bankrupt. Although adcon gel has been licensed by another company, it is no longer back on the market. So, one important tool that surgeons have to prevent scarring is not readily available.

    Another approach to preventing adhesive scarring of the spinal cord is to place biodegradable biomaterials between the spinal cord and arachnoid and between the arachnoid and dura. These materials should be able to prevent sticking and scarring between these layers. We are experimenting with such materials in the laboratory because we believe that this is critical for any therapy that requires exposure of the spinal cord for transplantation of cells.

    Finally, of course, when the surgeon is very careful in surgery to minimize the amount of the damage to the spinal cord and prevent blood leakage into the CSF during surgery, it is possible to avoid scarring. This is what is currently being done for the treatment of syringomyelia. Another possibility that has not been tested is to use high dose corticosteroids after surgery, known to prevent scarring, after surgery. A third possibility is to use some of the newer anti-scarring antibodies that are being developed be several companies. So, there are new treatments that are coming up that may be able to solve this problem.

    I hope that this has been useful. Please keep asking questions and I will keep editing and adding information to this topic to make it more understandable.

    Wise.

    [This message was edited by Wise Young on 06-19-05 at 09:08 AM.]

  2. #2
    So the idea of making two clean cuts to the spinal cord and bringing the ends together is definitely out?

  3. #3
    Originally posted by Chris2:

    So the idea of making two clean cuts to the spinal cord and bringing the ends together is definitely out?
    Chris2, it may be suitable for some purposes and under special circumstances. I want to suggest, however, that you should not think that you have no axons crossing the injury site.

    A majority of the "motor" axons that descend from the brain/brainstem to the lower spinal cord are inhibitory. They regulate movements that have been initiated by other axons. So, when people walk, their brains send the message to the spinal cord pattern generator to start getting excited. At the same time, the brain broadcasts a strong inhibitory message to neurons to tell them not to do anything until their posture is set and ready (otherwise people would fall). This entire setup takes about 200 milliseconds.

    Spinal cord injury may have damaged the spinal tracts that initiate the movement but many of the inhibitory tracts are still working. In such a person, the inhibitory state predominates in the spinal cord. The answer for such a person is to regenerate the excitatory, movement-initiating tracts. It makes no sense to cut out any inhibitory pathway that may remain.

    There is no guarantee that the starting from ground zero for regeneration will end up with better results than adding to the existing connections. Not only will transecting and reconnecting the spinal cord produce more scar tissue but the regenerated axons may not be as well connected as those that remain. Doesn't it seem to be a better idea to add to what survived?

    Wise.

  4. #4
    Junior Member pathfinder's Avatar
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    Dr Young,
    You're saying that in most cases where there has been damage to the spine with no scaring. So how do the stem cells know what,where and how to make a proper repair? Or are they the $64,000 questions?

  5. #5
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    So you basically saying that there are 3 different types of scar tissue; the adhesive,fibrous and glial scar. I hear you talking about possible solutions for the first two but I don't hear any possible solution for the glial scar. What about that?

  6. #6
    Pecla and Hoping,

    I disagree with the use of the word "scar" when applied to glia. As a former surgeon, scar to me means a fibrous collagenous scar. Just because there are many glial cells in a given area does not necessarily mean that it is a "scar". A scar physically obstructs axonal growth. I am not sure that a glial scar physically obstructs axonal growth. Please note that many of the regenerative therapies do not involve removal of the glial cells. For example, OEG transplants, chondroitinase, Nogo blockers, Nogo receptor blockers, cethrin (rho blocker), alternating electrical currents, the combination of Schwann-rolipram-dbcAMP, and other therapies that regenerate the spinal cord did not remove any glial cells from the injury site.

    Why do glial cells proliferate? What is the function of glia? If you read the textbooks, they will tell you that astrocytes support neurons. Actually, they do much more than that. Glial cells form the blood brain barrier. They identify and segregate the central nervous system from non-CNS tissues. For example, glial cells form "end-feet" that line all capillaries (blood vessels). The endfeet form tight junctions with each other, forming a barrier that prevents proteins, amino acids, and other molecules from passing through, so that molecules must be transported by the glial cells and then released by the glial cells to extracellular space of the spinal cord. Thus, glial proliferation is part of the repair of the spinal cord and rebuilding of the blood brain barrier.

    So, the concept of preventing glial scarring, in my opinion, may be misguided. Certainly, it is possible that too many glial cells may slow or even prevent axonal growth, but the evidence suggests that it is not the glial cells that prevent the axonal growth but an extracellular material called chondroitin-6-sulfate-glycoproteins (CSPG). Chondroitinase breaks down CSPG and allows axonal growth at the injury site.

    By the way, I want to say that the above is my opinion and may not necessarily be shared by other scientists. Many still subscribe to the theory that "glial scar" obstracts axonal growth. While I am certainly willing to reconsider the theory, I don't think that available evidence supports such a theory.

    So, I guess there are two reasons why I did not include a discussion of therapies that get rid of glial scars. The first is that I don't think that there are any therapies that eliminate glial scars. There are some therapies that inhibit the formation of glial scars shortly after injury but I am know of no effective therapy that reverses and eliminate "glial scar" after it has formed. The second is that I don't think that elimination of the glial scar is necessary or sufficient for regeneration.

    Wise.

  7. #7
    Dr. Young,

    What type of scar (if any) would there be in the case of a contusion type injury?

    No trama (like a car accident), no bleeding, no leakage of spinal fluid, just a unfortunate "bump" during scoli surgery. The lastest MRI (at 2 months post) shows a small bit of white matter on one side of the cord at the injury site, but nothing else, everything else looks normal, at least thats what the doc says.

    Sarah is almost 11 months post and we're at PW trying to get better. She can move everything, walking with a walker, but no B & B, and senses are still a bit screwed up. One side is definitely better than the other. She is now 14.

    Thanks for your response.

    Rick

  8. #8
    Senior Member alan's Avatar
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    The most recent doctor to look at my MRI said I have nothing but scar tissue between C-4 and C-6. Is he full of soup?

    Alan

    There's a fungus among us, and I'm not lichen it!

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  9. #9
    Originally posted by rickhemi:

    Dr. Young,

    What type of scar (if any) would there be in the case of a contusion type injury?

    No trama (like a car accident), no bleeding, no leakage of spinal fluid, just a unfortunate "bump" during scoli surgery. The lastest MRI (at 2 months post) shows a small bit of white matter on one side of the cord at the injury site, but nothing else, everything else looks normal, at least thats what the doc says.

    Sarah is almost 11 months post and we're at PW trying to get better. She can move everything, walking with a walker, but no B & B, and senses are still a bit screwed up. One side is definitely better than the other. She is now 14.

    Thanks for your response.

    Rick
    Rick,

    A contusion injury is usually associated with damage too the spinal cord, resulting in the loss of cells at the injury site. The area of cell loss initially shows up with microcysts (small holes left by cells that die) that may consolidate into a bigger cyst. Often (in rats about 70% of the time), glial cells invade into the injury area and fill it with a loose matrix of cells. Glial cells proliferate around the injury site. Inflammatory cells (macrophages and white blood cells) initially occupy the injury site. The extracellular space usually contains a substance called chondroitin-6-sulfate proteoglycans (CSPG). Axons that have been damaged usually die back a short distance and may grow back to the injury edge where they stop when they encounter CSPG. Usually, a thin rim of white matter (myelinated tissue) surrounds the injury site.

    If the white matter can be seen on MRI (as you describe for Sarah), it usually means that it is at least 1-2 mm or more thick. This is often sufficient to support some function on that side. From this description, I assume that Sarah has more feeling and movement on that side of the spinal cord. This usually results in a pattern of neurological deficits called the Brown-Secquard syndrome. The side that has some preserved white matter usually retains some sensation and motor control but has diminished pain and temperature sensation. The other side that has more damage may retain pain and temperature sensation.

    Most people with Brown-Secquard syndrome will recover walking. This is because there are enough axons on one side to activate the locomotor central pattern generator (CPG) that is located at about the L2 spinal cord level. The CPG activates patterned locomotor movements, including walking, loping, galloping, running, etc.

    You did not say the level of her spinal cord injury. I am surprised that she has no bowel and bladder function. Was her injury low (at about T12 vertebral level)? Are you sure that she does not have some bladder and anal sensation? Loss of bowel and bladder function would suggest damage to her lower sacral spinal cord (S2-S5).

    I think that it is a good idea for her to train at a place like Project Walk. This should improve her function.

    Wise.

  10. #10
    Thanks doctor Young for your detailed reply. Sarah's injury level is T-5, incl., almost 11 months post, and she's 14.

    She can sense when her blatter is very full, and she has always had sensation around the anal area. She has told me that her "most normal" sensation area is her groin area. But she still can not void herself yet.

    The initial MRI taken the day of injury came back inconclusive, but the one taken the next day showed the contusion, the neurologist said it was the size of a flame tip, very small.

    Now the pre-op MRI did showed a small syringst (?) in the lower level of her spine. He said that it did not cause her scoliosis, but was probably a symptom of the scoli. Sarah had a 71 degree angle in her back from scoli, which is why we had the operation to begin with, but it went terribly wrong, unfortunately.

    What do you think Dr. Young? Good prognosis or the standard "we'll see"?

    Thanks for your time.

    PS You're right, left side better than right (function), while the right side is more sensative.

    Rick

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