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Thread: Is restoration of blood flow necessary for regeneration

  1. #1
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    Is restoration of blood flow necessary for regeneration

    Quote Originally Posted by Wise Young View Post
    Dear Felice,

    The translator that you are using is not very good. So, let me rephrase you question as best as I can.

    Your question: You are pointing out many studies showing that recovery requires regrowth and reconnections of axons both above and below the injury site and such reconnection requires a variety of intrinsic and extrinsic factors to guide and influence reconnection. You ask whether I think that is it essential that we pay attention and use the data from all these studies to see the whole picture.

    Let me try to give the whole picture and not just the reconnection problem. For many years, scientists have been quite pessimistic about regeneration ever providing useful or functional improvements for the following reasons.

    First, they believed that spinal axons cannot regrow. This turns out to be mostly wrong. Many spinal axons can regrow if placed in the proper environment and given the appropriate growth factors. This was shown in a study by David and Aguayo in 1981, when they stuck a peripheral nerve into the spinal cord and observed many spinal axons grow into the peripheral nerve, all the way to the other end of the peripheral nerve stuck into another part of the spinal cord. Indeed, this was recently demonstrated in human when a peripheral nerve was inserted into the spinal cord of a human by Giorgio Brunelli, who showed that spinal axons grew into the peripheral nerve and all the way to the muscle which the peripheral nerve connected, entered the muscle and made synapses with the muscle. Furthermore, he showed that the synapses were not acetylcholinergic (which is the usual synapse between motoneurons and muscle) but glutamatergic (which is the synapse made by descending spinal axons and other neurons).

    Second, since the days of Sherrington who defined spinal reflexes in 1912, scientists and clinicians have thought that the spinal cord is pretty much hardwired, i.e. the axons had to go to specific places in order for the spinal cord to function. Wouldn't it be horrendous if the axons regenerated and you wriggled your toes when you tried to move your finger? Many scientists thought that this is what would happen, even if we were able to regrow the axons and reconnected them. Again, they turned out to be wrong because the spinal cord turns out to be much more plastic than they had every thought. Yes, regenerating axons do make many wrong connections. However, both the brain and spinal cord can learn. The last part is of particular interest because it is clear now that the spinal cord itself can learn. So, even when wrong connections are made, the brain and the spinal cord can "learn" the new circuitry and use it to operate the correct things. One of the most spectacular examples that I know of this is from Dr. Xiao, a urologist who connects the ventral roots of lumbar cord to the pudendal nerve. Amazingly, the axons from the lumbar roots (usually a part of the spinal cord that controls skeletal muscle) will grow into the pudendal nerve and reinnervate the bladder. After several months, if the person were to stimulate (i.e. scratch) the dermatome (skin) corresponding to the lumbar dermatome that was connected, that person can stimulate the bladder to contract and initiate micturition (the act of urination). This is proof of the amazing plasticity of the spinal cord.

    Third, it turns out that many motor programs are situated in the spinal cord. For example, the central pattern generator (CPG) is located around the L2 spinal cord. When we walk, we tell that CPG to start walking. If we want to trot, gallop, or run, we just activate the CPG harder. In fact, we don't even have to do this with specific connections. Scientists have shown in cats and other animals that it is possible to do this by dripping neurotransmitters onto the lower spinal cord. The spinal cord does most of the coordination and reflexes and the brain simply tells the system to activate the programs.

    Fourth, most people with severe incomplete spinal cord injury are paralyzed for a period of time, perhaps 6-12 months, before they recover their motor function. These people often have lost as much as 80-90% of their spinal cord. However, they can walk with 10% of their cord. It takes practice. In fact, what they are really doing is teaching the spinal cord to get use to newer and fewer connections.

    So, in summary specificity of reconnection is not essential for recovery of function. Of course, the more you have, the faster you will recover but many people have recovered with remarkably few of their axons. And many look so functional, you would not believe that they have been spinal injured, much less paralyzed for many months or even years. If you have not read the story of Patrick Rummerfield, you should. This man runs the world's ultra-marathons today but he was almost completely quadriplegic for over a year. Most people who meet him would not know that he was severely spinal-injured.

    Wise.
    Quick question: I am hopeful that regrowth can happen, but in my boyfriend's case, we think that the artery of Adamkiewicz is gone (did not appear on the angiogram) --does regrowth require a blood supply to be restored first?

    Thanks,
    m.

  2. #2

    Is restoration of blood flow necessary for regeneration

    Quote Originally Posted by VBNoon View Post
    Quick question: I am hopeful that regrowth can happen, but in my boyfriend's case, we think that the artery of Adamkiewicz is gone (did not appear on the angiogram) --does regrowth require a blood supply to be restored first?

    Thanks,
    m.
    I don't know the answer to your question.

    Based on your earlier description of transverse myelitis in your friend, the absence of the artery of Adamkiewicz suggests that he might have embolized or occluded that artery. The distribution of blood supply to the spinal cord is extremely variable. According to Takase, et al. (Source), in 75% of people, the artery enters the spinal cord at at T9-11 and occasionally may enter in the lumbar level. About a quarter of people may have two such arteries. I did not see this study until just now and the results conflict with my own experience from the 1980's, doing somatosensory evoked potential monitoring of people during embolization of people with arteriovenous malformation. I remember the artery entering the spinal at T4-8 levels. In any case, the anterior artery syndrome usually results in loss of motor function, including bladder and anal sphincters but often with some preservation of sensory function. Is this the case with your friend?

    Wise.
    Last edited by Wise Young; 02-08-2010 at 05:22 PM.

  3. #3
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    Thank you Dr. Young. He is T7 complete -- no sensory, no motor, no reflexes. On the most recent MRI, the doctor said that the spinal cord looked necrotic for at least 5 segments and he is now 18 months post-injury. We are going to the neurologist tomorrow to review the angiogram and MRI again, so I'll definitely ask him what looks to be missing in case I have not identified it properly.

    Thanks,
    m.

  4. #4
    Quote Originally Posted by VBNoon View Post
    Thank you Dr. Young. He is T7 complete -- no sensory, no motor, no reflexes. On the most recent MRI, the doctor said that the spinal cord looked necrotic for at least 5 segments and he is now 18 months post-injury. We are going to the neurologist tomorrow to review the angiogram and MRI again, so I'll definitely ask him what looks to be missing in case I have not identified it properly.

    Thanks,
    m.
    VBNoon, I thought that it would be better to put your question into a separate thread for continuing discussion.

    Wise.

  5. #5
    Let me try to explain why I said that I don't know. Obviously, blood flow is necessary for tissues to function and therefore essential for regeneration. However, it is not clear that there is a shortage of blood supply to the chronically injured spinal cord.

    If one looks at the injury site of the spinal cord shortly after injury, it is usually pale and looks short of blood supply. This may be because the cord itself is edematous (swollen) and ischemia (has low blood flow). In chronically injured spinal cord, unless there is continuing compression of the spinal cord, there is often more blood vessels at the injury site.

    Angiogenesis (formation of new blood vessels) occur in the spinal cord after injury. However, most of the information comes from traumatized spinal cord and I don't know of many (any) pathological studies of infarcted (necrotic) spinal cords. It should be of interest to do a tracer MRI study to see what the blood flow is in at the infarcted site of the spinal cord.

    Wise.

  6. #6
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    Hi Dr. Young,

    Thanks for your comments. Our neurosurgeon's response (I showed him this thread) was that there is no good way to surgically restore blood flow due to the microscopic arterties that are involved. He did not think that a tracer MRI study would be of any benefit, since the damage has already been done.

    I still have hope that there will be some regeneration, although we will probably have to wait for a therapy to be developed in order to see any (however slight) recovery. We hope to come to the Rutger's open house in March!

    Thanks,
    m.

  7. #7
    Quote Originally Posted by VBNoon View Post
    Hi Dr. Young,

    Thanks for your comments. Our neurosurgeon's response (I showed him this thread) was that there is no good way to surgically restore blood flow due to the microscopic arterties that are involved. He did not think that a tracer MRI study would be of any benefit, since the damage has already been done.

    I still have hope that there will be some regeneration, although we will probably have to wait for a therapy to be developed in order to see any (however slight) recovery. We hope to come to the Rutger's open house in March!

    Thanks,
    m.
    Good, I will see you in about two weeks. Wise.

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