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

  1. #41
    Quote Originally Posted by Princess "Leia"
    That day Wise I was very motivated by our most important mission(CRPA), on major medications and at days end payed very dearly for pushing myself way to hard. It was worth it all! By the way, do you recall meeting Congressman Mark Foley with me that same afternoon?

    Pam
    Pam,

    I must not have been in on that meeting. If so, I don't remember him at all.

    Wise.

  2. #42

    Fischer 344 rats do NOT make a proper scar

    Quote Originally Posted by Wise Young
    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.
    The paper my lab recently published in Journal of Biology describes experiments in which we compared scar formation and cavitation in Fischer 344 rats, the highly inbred strain of rat used in the Tuszynski paper, with Sprague Dawley rats, a commonly used outbred strain. We had originally wanted to use just the Fischer rats in our GDA / SCI transplantation studies because they more closely matched our donor strain of rats. However we found that they did not form anywhere near as robust a fibrotic astroglial scar as the Sprague Dawley rats when given an identical injury. Instead they formed a more extensive and irregular shaped macrophage filled cavity, a result which fits with current thinking that scar tissue forms as a protective barrier to prevent further damage to surrounding tissue from toxic inflammation within the injury site. In effect this strain of rats does not make as much scar tissue as a more normal outbred rat strain. Of course it is difficult to assess which rat strain more closely matches scar formation in humans. However it is generally thought that scarring is robust in humans (remember it is protective) and as most humans are not inbred I would expect them to more closely match the Sprague Dawley rats. So why don't the Fischer rats recover from SCI better than Sprague Dawleys if they don't make as robust of a scar? Well despite the likelyhood of extra axon sprouting at the site of injury they are also more likely to have secondary damage to tissue surrounding the injury site with an asociated loss of function.

    It has also long been known that axons have the ability to sprout into chronic scar tissue, even in Sprague Dawley rats. My lab has shown that the levels of inhibitory proteoglycans actually drops in chronic scar tiisue which correlates nicely with the increased sprouting. Scar tissue changes with time and is not an absolute barrier to growth but is rather a major impediment. Several labs have published major differences in reaction to SCI in different strains of mice and as I mentioned, my lab has published a similar diiference in two strain of rats. To my mind it is not prudent to make a sweeping statement about scar formation if it is just based on SCI in one, inbred strain of rat.

  3. #43
    Quote Originally Posted by Wise Young
    Pam,

    I must not have been in on that meeting. If so, I don't remember him at all.

    Wise.
    Wise, thats the first sign of old age, forgetfulness.

    Yep, it was you, me and the lovely Susanne Poon. When we were done at the Foley appoinment we all scooted over to see Senator Latenberg. Remember? It's ok if you don't, there was so much goin on that day but I ws so grateful to have you both by my side.

    Pam

  4. #44
    Quote Originally Posted by Stephen Davies
    The paper my lab recently published in Journal of Biology describes experiments in which we compared scar formation and cavitation in Fischer 344 rats, the highly inbred strain of rat used in the Tuszynski paper, with Sprague Dawley rats, a commonly used outbred strain. We had originally wanted to use just the Fischer rats in our GDA / SCI transplantation studies because they more closely matched our donor strain of rats. However we found that they did not form anywhere near as robust a fibrotic astroglial scar as the Sprague Dawley rats when given an identical injury. Instead they formed a more extensive and irregular shaped macrophage filled cavity, a result which fits with current thinking that scar tissue forms as a protective barrier to prevent further damage to surrounding tissue from toxic inflammation within the injury site. In effect this strain of rats does not make as much scar tissue as a more normal outbred rat strain. Of course it is difficult to assess which rat strain more closely matches scar formation in humans. However it is generally thought that scarring is robust in humans (remember it is protective) and as most humans are not inbred I would expect them to more closely match the Sprague Dawley rats. So why don't the Fischer rats recover from SCI better than Sprague Dawleys if they don't make as robust of a scar? Well despite the likelyhood of extra axon sprouting at the site of injury they are also more likely to have secondary damage to tissue surrounding the injury site with an asociated loss of function.

    It has also long been known that axons have the ability to sprout into chronic scar tissue, even in Sprague Dawley rats. My lab has shown that the levels of inhibitory proteoglycans actually drops in chronic scar tiisue which correlates nicely with the increased sprouting. Scar tissue changes with time and is not an absolute barrier to growth but is rather a major impediment. Several labs have published major differences in reaction to SCI in different strains of mice and as I mentioned, my lab has published a similar diiference in two strain of rats. To my mind it is not prudent to make a sweeping statement about scar formation if it is just based on SCI in one, inbred strain of rat.
    Stephen, I agree with you. A lot of sweeping assumptions have been made about "scar" in the spinal cord and I don't think that we know enough to assume that the primary obstacle to regeneration in human spinal cord injury is due to collagenous scars.

    The type of injury also may make a big difference. Penetrating wounds may be different than contusion injuries, allowing the entry of fibroblasts into the spinal cord from surrounding tissues. Do you see fibroblast and collagen deposits in the spinal cord after stab wounds?

    Yes, I was aware of your earlier paper on that subject and was interested to find that you found more variable responses to stab wounds in the Fischer rat. We have recently developed a GFP Fischer rat as a donor source of cells and will be starting to look at spinal cord contusion in the Fischer rat.

    I have always used outbred rats, either the Sprague-Dawley or the Long-Evans hooded rats.

    Wise.

  5. #45
    I love these scar posts. Thanks guys

    Cripply, scared and scarred

  6. #46
    Quote Originally Posted by Princess "Leia"
    Wise, thats the first sign of old age, forgetfulness.

    Yep, it was you, me and the lovely Susanne Poon. When we were done at the Foley appoinment we all scooted over to see Senator Latenberg. Remember? It's ok if you don't, there was so much goin on that day but I ws so grateful to have you both by my side.

    Pam
    Pam,

    Maybe I am getting Alzheimer's but I have been more than a little absent-minded all my life. Suzanne with with us when we met Foley? Hmmm, I have always told Suzanne that if she hung around us that she would meet interesting people. We still chuckle about how a couple of Hell's Angels agreed to escort us out of Baltimore when we got lost in after visiting John McDonald.

    Wise.

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