Originally posted by 6 Shooter
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Very few people have seen a "glial scar" in human. Richard Bunge probably looked at more chronically injured human spinal cords than any other scientist before he died. I remember looking at some of the spinal cords once when I visited him at the Miami Project. I remember seeing a lot of macrophages in a spinal cord of a woman who died more than 20 years after injury. He also showed me axons with bulbous terminals at the injury edge, suggesting that the axons are still trying to grow and are showing signs of what Jerry Silver has called "frustrated axons". There were glial cells around and within the lesion site.
I have looked at many (hundreds) of contused rat spinal cords. In almost all of the spinal cords (6-14 weeks after contusion), gliosis (increased GFAP staining) around the injury site and a loose matrix of GFAP positive cells within the injury site. If a true cavity were present (usually lined with ependymal cells) at the injury site, there is usually a astrocytic lining at the borders of the cavity. However, these are relatively rare. We see them only in 20% or so of the spinal cords and there is almost always a rim of white matter around the cavity through which axons should be able to grow.
In very severely injured human spinal cords, there may be little tissue left at the injury site. Usually, these spinal cords have been crushed and have not been decompressed for long periods. The injury site is severely atrophied and much scar tissue outside of the spinal cord constrict the cord. In these cases, if the "scar" constricting the spinal cord is removed, the spinal cord expands. Scar outside of the spinal cord may tether the cord. These are usually wispy and barely visible at surgery, easily removed by just sweeping the surface of the cord with an instrument or even cotton swab.
I have seen the histology of the injury site from human spinal cords shown by Carlos Lima at a meeting Vancouver about a decade ago. He and his colleagues had cut out the injury site and did histology on the tissue that they removed. He showed pictures of tissue that had thousands of silver-stained axons in the sections. That really shocked me. I don't remember seeing any GFAP stained section and did not see anything that looks like a glial scar/barrier.
In my opinion, there is simply not enough evidence from human spinal cords that would justify the surgical of "glial scar" inside the spinal cord. Yes, there is evidence of gliosis but many studies have already shown that gliosis alone does not present physical barrier to axon growth. More important, I am not sure that the surgery to remove the "glial scar" would actually result in formation of a true glial scar, i.e. meningeal fibroblasts invading into the cut site and astrocytes walling off these fibroblasts.
The presence of terminal axonal bulbs at the injury edges, seen by Richard Bunge and colleagues at the Miami project, does suggest that CSPG is present and the axons are stopping their growth and forming the terminal bulbs. This justifies, for example, the use of chondroitinase or CSPG receptor blocker, to see such treatments would facilitate axon growth. But, I have not seen evidence of a physical glial scar that would warrant surgical removal of the injury site.
There are some who says that since axons are not growing across the injury site, why not just remove the injury site and put something more conducive to axon growth at the injury site. While they usually use the excuse of "glial scar" to say that lesion site should be removed, what they really want is to show that their biomaterial is better than the injury site for supporting axon growth. Since the Kunming group showed that intradural decompression improves locomotor recovery in patients with subacute spinal cord injury, we have been thinking that the cavity left behind after removing necrotic tissue would be an excellent place to put biomaterial.
I recently heard the presentation of a scientist who believes wants to put a biomaterial into the spinal cord. We have been evaluating different biomaterials that can be put into the cavity of subacute injured spinal cord. These include the self-assembling peptide (SAP), different hydrogels, and other materials that may contain growth factors. In the coming year, we are hoping to initiate a multicenter phase III trial to confirm that subdural decompression and intensive locomotor training restore locomotor function in patients with ASIA A complete spinal cord injuries. I am hoping that we can then initiate trials of various biomaterials placed into the cavity.
Wise.
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