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.
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.]
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.
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.]
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