Doctors in China carry out world first spine surgery

[Nowhere Man]

Peripheral nerves can (they don't always, but often can) regenerate quite nicely, given certain circumstances, and their neuronal cell bodies are in the spinal cord. There are many different kinds of neurons but at least some of them can grow their axons after injury, following a "bridge", as you propose, of schwann cells.

Peripheral nerves are irrelevant. They are not the central nervous system (brain & spinal cord). Intrinsically, the brain & spinal cord do not regenerate. Any regrowth of spinal cord axons after treatment are extremely low percentage and very short distance. Oh, except umbilical cord blood cells + lithium! They regenerated from cervical down to cpg (very very far distance)...as believed by Dr. Young.

[Nowhere Man]

Seem Dr. Silvers peptide was able to get the axons to move in rat models. I believe that yes axons don't know where to go, but I believe with very intensive constant functional rehab , That the body can be rewired sort to speak. Dr. Young and a lot of the researchers in China have stated this is vital after any treatment that is why!

How many axons (all, a lot, a tiny fraction?) and how far? Images?

[tomsonite]

Tom, you are right, it is open for debate, but when several scientist's studies (Kai Liu, Paul Lu, & others) have documented rivers of axons growing through animal injury sites, it is completely inaccurate to state that glial scars prevent regeneration. I'm confused why researchers are talking about cutting out the 'scar' when there is concrete evidence it is not necessary.

Jim, I don't necessarily disagree with those sentiments. However, you and Wise often say the scar is not a barrier to regeneration, yet I still haven't seen an alternative theory proposed. What is it that you/Wise think IS the barrier to regeneration after spinal cord injury?

[tomsonite]

Peripheral nerves can (they don't always, but often can) regenerate quite nicely, given certain circumstances, and their neuronal cell bodies are in the spinal cord. There are many different kinds of neurons but at least some of them can grow their axons after injury, following a "bridge", as you propose, of schwann cells.

Peripheral nerves are irrelevant. They are not the central nervous system (brain & spinal cord). Intrinsically, the brain & spinal cord do not regenerate. Any regrowth of spinal cord axons after treatment are extremely low percentage and very short distance. Oh, except umbilical cord blood cells + lithium! They regenerated from cervical down to cpg (very very far distance)...as believed by Dr. Young.

I'll re-state the bolded text in my first post...the neuronal cell bodies of peripheral axons are in the spinal cord - they ARE in the central nervous system.

You said "adult neurons don't regenerate their axons". This is not always true. There are no neuronal cell bodies in the peripheral nervous system - only neuronal cell bodies in the CNS that have axons that branch out into the peripheral nervous system.
To say that the "brain and spinal cord" don't regenerate is oversimplifying it, since there are a multitude of different type of tissues, and an injury to the PNS creates a very different cellular environment than an injury to different parts of the CNS.
I don't think the lack of axonal regeneration after SCI can solely be explained by a lack of intrinsic growth capacity, since some axons (whose roots are in the spinal cord) clearly can regenerate.

[Nowhere Man]

Just because a peripheral motor neuron starts in the CNS does not make it equivalent to a motor neuron that starts in the brain! Peripheral nerves are different than brain / spinal cord nerves. Even different neurons solely inside the central nervous system have different genetic makeup. That's why only certain axon tracts regenerate with PTEN, while others don't.

I didn't say it was the sole reason. However, it is imo, a significant reason, and one that must be overcome.

[Nowhere Man]

Just because a peripheral motor neuron starts in the CNS does not make it equivalent to a motor neuron that starts in the brain! Peripheral nerves are different than brain / spinal cord nerves. Even different neurons solely inside the central nervous system have different genetic makeup. That's why only certain axon tracts regenerate with PTEN, while others don't.

I didn't say it was the sole reason. However, it is imo, a significant reason, and one that must be overcome in order to achieve any robust regeneration .

[tomsonite]

There is a lack of a cellular bridge for axons to travel.

Most importantly, is that adult neurons don't regenerate their axons. It is genetic. You can get rid of any scar obstruction, provide a beautiful bridge to cross, but the axons would still not move. You may find proof of .0001% that may move a few mm's but the overwhelming majority intrinsically do not move. This is why genetic therapy is really the only way to get host axons to regenerate, imo.

Even if you could get them to miraculously regenerate, they wouldn't know where to go. SCI is like a brain injury, only with the cord (same tissue as brain).

Just because a peripheral motor neuron starts in the CNS does not make it equivalent to a motor neuron that starts in the brain! Peripheral nerves are different than brain / spinal cord nerves. Even different neurons solely inside the central nervous system have different genetic makeup. That's why only certain axon tracts regenerate with PTEN, while others don't.

I didn't say it was the sole reason. However, it is imo, a significant reason, and one that must be overcome.

You said above adult neurons don't regenerate their axons. I think that is too broad of a statement, because CNS neurons can regenerate their axons given the right environment (peripheral NS) and cellular circumstances (type of glial cell, mechanism/severity of original injury, etc).
You say "peripheral nerves are different than brain/spinal cord nerves", which is also too broad of a statement. A peripheral axon comes from a central neuron. There are no peripheral "nerves", only peripheral axons whose neuronal cell bodies are in the spinal cord (or lower parts of the brain if we're talking cranial nerves). If a peripheral axon is severed, the neuron from which it comes (an adult neuron located in the spinal cord, i.e. in the central nervous system) can regenerate the axon given the right circumstances. People fully recovery from brachial plexus injuries all the time. A brachial plexus injury quite literally is an injury to a peripheral axon. How can people naturally recover from those injuries if the neuronal cell bodies in the spinal cord are not able to regenerate those axons?

A motor neuron that starts in the brain (an upper motor neuron) is obviously different than a motor neuron that starts in the spinal cord (a lower motor neuron). Obviously, a corticospinal axon is much harder to regenerate, but propriospinal axons have shown robust regeneration with functional outcomes without gene therapy in an animal model. The introduction from this paper sums it up nicely:

"Classic studies have repeatedly demonstrated (Ramon y Cajal, 1928; Aguayo et al., 1981) that a favorable environment for CNS axon regrowth can be created by engraftment of a segment of peripheral nerve, which can be further augmented via the addition of growth factors (Cheng et al., 1996; Lee et al., 2002b; Tsai et al., 2005). However, the lack of significant exodus of axons from the graft had derailed the use of the peripheral nerve bridging strategy since it was first implemented by Tello in Ramon y Cajal's laboratory nearly a century ago (Ramon y Cajal, 1928). Importantly, recent papers have shown that a buildup of inhibitory reactive glial-derived chondroitin sulfate proteoglycans (CSPGs) at the peripheral nervous system (PNS)/CNS interfaces is a major impediment that curtails regenerating axons from entering but especially exiting the bridge (Houle et al., 2006; Yang et al., 2006; Busch and Silver, 2007; Alilain et al., 2011).
...
We provide physiological, anatomical, and pharmacological evidence of a surprising degree of regeneration from particular brainstem centers past the distal graft/cord interface, with some axons reaching all the way to lumbo-sacral levels and with return of bladder control."

Source: Lee Y-S, Lin C-Y, Jiang H-H, DePaul M, Lin VW, Silver J. Nerve Regeneration Restores Supraspinal Control of Bladder Function after Complete Spinal Cord Injury. The Journal of Neuroscience. 2013;33(26):10591-10606. doi:10.1523/JNEUROSCI.1116-12.2013.

So yes, the CNS axons may have trouble leaving the peripheral nerve graft, but they can enter and grow along the nerve graft without any spurring along from gene re-engineering.

It would seem there is a LOT of evidence to support the idea that some kinds of neurons CAN regenerate their axons if provided the right environment, whether in the periphery or the central nervous system. This is not to say that axonal regeneration isn't a significant obstacle, as it can still (and obviously needs) to be enhanced. But for many kinds of axons, it seems that the environment in the CNS and/or injury site is a more significant obstacle to regeneration.

[Nowhere Man]

You said above adult neurons don't regenerate their axons. I think that is too broad of a statement, because CNS neurons can regenerate their axons given the right environment (peripheral NS) and cellular circumstances (type of glial cell, mechanism/severity of original injury, etc).
You say "peripheral nerves are different than brain/spinal cord nerves", which is also too broad of a statement. A peripheral axon comes from a central neuron. There are no peripheral "nerves", only peripheral axons whose neuronal cell bodies are in the spinal cord (or lower parts of the brain if we're talking cranial nerves). If a peripheral axon is severed, the neuron from which it comes (an adult neuron located in the spinal cord, i.e. in the central nervous system) can regenerate the axon given the right circumstances. People fully recovery from brachial plexus injuries all the time. A brachial plexus injury quite literally is an injury to a peripheral axon. How can people naturally recover from those injuries if the neuronal cell bodies in the spinal cord are not able to regenerate those axons?

The nerve (axons) are part of a neuron.

You are taking the fact that I said "adult neurons don't regenerate" and are running with it. I was being general. I meant neurons fully within the brain and spinal cord do not (aka spinal cord injury). Yes, peripheral nerves, that branch out of spinal cord (but extend out to body), can regenerate. They are different cells. I don't care if their cell nucleus starts in spinal cord, that is irrelevant. When your peripheral nerve gets injured, your body, is genetically programmed to regenerate, whereas a spinal cord injury is genetically programmed to not.

I have never seen images of robust regeneration of spinal cord axons. Could you provide me with some? Are you talking about like .001% of axons regenerating? I have never seen 25-100% of axons regenerating even a cm. Wouldn't a scaffold bridge, nerve bridge, and/or chase to clear the 'scar' create an environment that then gets robust regeneration (25-100%)?

I agree that environment is a factor. But the prettiest environment (to an axon) won't mean sh*t to the spinal cord without an intrinsic push, again, imo.

A motor neuron that starts in the brain (an upper motor neuron) is obviously different than a motor neuron that starts in the spinal cord (a lower motor neuron). Obviously, a corticospinal axon is much harder to regenerate, but propriospinal axons have shown robust regeneration with functional outcomes without gene therapy in an animal model. The introduction from this paper sums it up nicely:

"Classic studies have repeatedly demonstrated (Ramon y Cajal, 1928; Aguayo et al., 1981) that a favorable environment for CNS axon regrowth can be created by engraftment of a segment of peripheral nerve, which can be further augmented via the addition of growth factors (Cheng et al., 1996; Lee et al., 2002b; Tsai et al., 2005). However, the lack of significant exodus of axons from the graft had derailed the use of the peripheral nerve bridging strategy since it was first implemented by Tello in Ramon y Cajal's laboratory nearly a century ago (Ramon y Cajal, 1928). Importantly, recent papers have shown that a buildup of inhibitory reactive glial-derived chondroitin sulfate proteoglycans (CSPGs) at the peripheral nervous system (PNS)/CNS interfaces is a major impediment that curtails regenerating axons from entering but especially exiting the bridge (Houle et al., 2006; Yang et al., 2006; Busch and Silver, 2007; Alilain et al., 2011).
...
We provide physiological, anatomical, and pharmacological evidence of a surprising degree of regeneration from particular brainstem centers past the distal graft/cord interface, with some axons reaching all the way to lumbo-sacral levels and with return of bladder control."

Source: Lee Y-S, Lin C-Y, Jiang H-H, DePaul M, Lin VW, Silver J. Nerve Regeneration Restores Supraspinal Control of Bladder Function after Complete Spinal Cord Injury. The Journal of Neuroscience. 2013;33(26):10591-10606. doi:10.1523/JNEUROSCI.1116-12.2013.

So yes, the CNS axons may have trouble leaving the peripheral nerve graft, but they can enter and grow along the nerve graft without any spurring along from gene re-engineering.

It would seem there is a LOT of evidence to support the idea that some kinds of neurons CAN regenerate their axons if provided the right environment, whether in the periphery or the central nervous system. This is not to say that axonal regeneration isn't a significant obstacle, as it can still (and obviously needs) to be enhanced. But for many kinds of axons, it seems that the environment in the CNS and/or injury site is a more significant obstacle to regeneration.

In that Dr. Silver study, what % of axons regenerated. Axons from all spinal tracts or just one or two? Did sensory axons also regenerate through the newfound friendly environment? I'm not convinced at all that bladder function was even restored.

[tomsonite]

The nerve (axons) are part of a neuron.

You are taking the fact that I said "adult neurons don't regenerate" and are running with it. I was being general. I meant neurons fully within the brain and spinal cord do not (aka spinal cord injury). Yes, peripheral nerves, that branch out of spinal cord (but extend out to body), can regenerate. They are different cells. I don't care if their cell nucleus starts in spinal cord, that is irrelevant. When your peripheral nerve gets injured, your body, is genetically programmed to regenerate, whereas a spinal cord injury is genetically programmed to not.

I have never seen images of robust regeneration of spinal cord axons. Could you provide me with some? Are you talking about like .001% of axons regenerating? I have never seen 25-100% of axons regenerating even a cm. Wouldn't a scaffold bridge, nerve bridge, and/or chase to clear the 'scar' create an environment that then gets robust regeneration (25-100%)?

I agree that environment is a factor. But the prettiest environment (to an axon) won't mean sh*t to the spinal cord without an intrinsic push, again, imo.



In that Dr. Silver study, what % of axons regenerated. Axons from all spinal tracts or just one or two? Did sensory axons also regenerate through the newfound friendly environment? I'm not convinced at all that bladder function was even restored.

I know that axons are part of a neuron...you seem to be using the words "nerve", "axon", and "neuron" interchangeably which is why I was trying to clarify.

Saying it is intrinsic that adult neurons don't regenerate their axons is not being general. It is being quite specific.

ALL neurons are fully within the brain or spinal cord. There are no neurons in the peripheral nervous system. You are talking about axons that don't regenerate.

The neuronal nucleus being in the spinal cord is NOT irrelevant. They provide proof that adult neurons can regenerate their axons.

A spinal cord injury not being able to naturally regenerate does not mean that all neurons are genetically programmed to not regenerate their axons after injury. The CNS is a much different environment than the PNS and that is a much bigger factor than you are giving it credit for. You say that the prettiest environment "won't mean shit to the spinal cord...imo". Well, what is your opinion based off of? What actual evidence can you present to me besides your own opinion? Just because you haven't seen axons regenerate long distances doesn't mean it's an intrinsic capacity of neurons to not regenerate their axons.

A scaffold bridge, nerve bridge, or ch'ase would NOT create an environment that gets robust regeneration (in fact, in the source I cited, it talked about how a nerve bridge alone doesn't create significant nerve regeneration). There are way more factors than that which are involved in creating a favorable environment for axons to grow. Once again, you are over simplifying. You are not taking into account how to organize oligodendrocytes or astrocytes, two complex cells that are not found in the PNS. You are not taking into account the neuronal cell bodies that might have died when the CNS was injured. You are not taking into account proteins like PCAF, which are found in the peripheral nervous system that allow for axonal regeneration, but are not found in the CNS. And even then, as you and I both have already stated, SOME neurons are intrinsically able to grow axons better than others (corticospinal tract vs. propriospinal tract, for example).

The paper by Dr. Silver is public access.
http://www.ncbi.nlm.nih.gov/pubmed?t...0propriospinal

I don't know what % of axons regenerated, it clearly wasn't a high percentage. However, the axons regenerated a long distance (relative to the size of the animal) and significant, but not full, bladder function was restored.

[Nowhere Man]

1)

?The neuronal nucleus being in the spinal cord is NOT irrelevant. They provide proof that adult neurons can regenerate their axons.?

I'm not making the statement that no adult neurons can regenerate. You are arguing semantics. When I said 'adult neurons', I was being general, as this is an online board of non-specialists. The neurons in the brain & spinal cord that make up the spinal cord tracts do not regenerate (That is why we are in wheelchairs for life). Those are the adult neurons I was talking about. I don't care if neurons with peripheral nerves regenerate and they have a nucleus in the spinal cord. They are different neurons with a different purpose. The fact that they regenerate doesn't prove one way or another if environment vs intrinsic capacity is the bigger cause for why spinal cord axons don't regenerate. That is why it is irrelevant.

Axons are part of the neuron. Nerves are collections of axons. So I often interchange the terms.

2)

?corticospinal axon is much harder to regenerate, but propriospinal axons have shown robust regeneration with functional outcomes without gene therapy in an animal model.?

Well how do you define robust? Compared to a control (basically 0 axons) or compared to the total number of propriospinal axons? The images in paper didn't look robust to me. Nor is there any concrete proof of recovery of function. I would love to see a nice clear visual of this robust axon growth, with same point of view as the one in the link. Even if it were true, only 1 spinal tract out of what 15?

3)

?A spinal cord injury not being able to naturally regenerate does not mean that all neurons are genetically programmed to not regenerate their axons after injury. The CNS is a much different environment than the PNS and that is a much bigger factor than you are giving it credit for. You say that the prettiest environment "won't mean shit to the spinal cord...imo". Well, what is your opinion based off of? What actual evidence can you present to me besides your own opinion? Just because you haven't seen axons regenerate long distances doesn't mean it's an intrinsic capacity of neurons to not regenerate their axons."

Try not to get bogged down by 'All'. If just 1 axon out of millions/billions regenerates, then 'Some' axons can regenerate. Which of course means nothing. My opinion is based on scientists who are looking into Gene therapy to cure SCI. Especially from Dr. Murray Blackmore. In fact my next point is taken straight from him. Embryonic neurons can grow axons even in a hostile SCI environment. For example, embryonic neurons implanted into 14 day complete SCI were able to grow axons far and in great amount (visually) through a hostile SCI. Here is an excerpt from Mark Tuszynski's 2012 paper: "Long-Distance Growth and Connectivity of Neural Stem Cells After Severe Spinal Cord Injury" :

"Thus, properties intrinsic to early stage neurons can overcome the inhibitory milieu of the injured adult spinal cord to mount remarkable axonal growth resulting in formation of novel relay circuits that significantly improve function."


Here is a beautiful, clear image of axon growth through hostile environment. (it won't let me paste image).

Link --> http://www.ncbi.nlm.nih.gov/pmc/arti...432/figure/F6/

So when Dr. Steward tried to replicate the Neural Stem Cells + Fibrin, he says that the EMBRYONIC neurons extended axons very far & plentiful inside a hostile SCI environment. But NOT the adult host neurons.

Exp Neurol. 2014 Jul;257:186-204. doi: 10.1016/j.expneurol.2014.04.008. Epub 2014 Apr 18. ?A re-assessment of long distance growth and connectivity of neural stem cells after severe spinal cord injury.? Sharp KG1, Yee KM1, Steward O2.

"There was extensive outgrowth of GFP labeled axons from the graft (embryonic stem cell neurons), but there was minimal ingrowth of host axons (host adult neurons) into the graft revealed by tract tracing and immunocytochemistry for 5HT. There were no statistically significant differences between transplant and control groups in the degree of locomotor recovery. Our results confirm the previous report that NSC transplants can fill lesion cavities and robustly extend axons, but reveal that most grafts do not create a continuous bridge of neural tissue between rostral and caudal segments."

[Nowhere Man]

4)

A scaffold bridge, nerve bridge, or ch'ase would NOT create an environment that gets robust regeneration (in fact, in the source I cited, it talked about how a nerve bridge alone doesn't create significant nerve regeneration). There are way more factors than that which are involved in creating a favorable environment for axons to grow. Once again, you are over simplifying. You are not taking into account how to organize oligodendrocytes or astrocytes, two complex cells that are not found in the PNS. You are not taking into account the neuronal cell bodies that might have died when the CNS was injured. You are not taking into account proteins like PCAF, which are found in the peripheral nervous system that allow for axonal regeneration, but are not found in the CNS. And even then, as you and I both have already stated, SOME neurons are intrinsically able to grow axons better than others (corticospinal tract vs. propriospinal tract, for example).

I hear a lot of talk about scar being a barrier. Ok. Chase or Dr. Silver’s peptide breaks down that barrier (so they say). No robust regeneration. I hear about a lack of a bridge being a barrier. So there have been scaffolds and nerve grafts. Yet I have seen no robust regeneration of host axons. I fully understand that the environment is more complex than that. Yet with neural stem cells and fibrin, I see robust axon growth through a hostile spinal cord environment but only from embryonic stem cells. So fibrin + other non-neuronal neural stem cells (added environment) is a good enough environment for embryonic neurons but not host adult neurons. This leads me to have the OPINION that the intrinsic factors that prevent axon growth of adult host spinal tracts are stronger (not the only) factors than a hostile environment. By a lot.

5) So what is your opinion based on? Just that peripheral nerves regenerate?

[paolocipolla]

4)

I hear a lot of talk about scar being a barrier. Ok. Chase or Dr. Silver’s peptide breaks down that barrier (so they say). No robust regeneration. I hear about a lack of a bridge being a barrier. So there have been scaffolds and nerve grafts. Yet I have seen no robust regeneration of host axons. I fully understand that the environment is more complex than that. Yet with neural stem cells and fibrin, I see robust axon growth through a hostile spinal cord environment but only from embryonic stem cells. So fibrin + other non-neuronal neural stem cells (added environment) is a good enough environment for embryonic neurons but not host adult neurons. This leads me to have the OPINION that the intrinsic factors that prevent axon growth of adult host spinal tracts are stronger (not the only) factors than a hostile environment. By a lot.

5) So what is your opinion based on? Just that peripheral nerves regenerate?

One aspect that could be very important is what signals from the injured axon (injury site) get to the cell body. It seems that in the PNS you have different signals than in the CNS traveling to the cell body that cause a cascade of events that result in regneration of the axon. It is probably more complex than this, but that seems a possible part of the problem..

[Nowhere Man]

One aspect that could be very important is what signals from the injured axon (injury site) get to the cell body. It seems that in the PNS you have different signals than in the CNS traveling to the cell body that cause a cascade of events that result in regneration of the axon. It is probably more complex than this, but that seems a possible part of the problem..

I agree. I also think those signals would be vital to guiding a regenerated axon, because they have no idea where to go. It just goes to show how highly complex a problem like SCI truly is, and how far away an effective treatment really is. People need to stop looking at the finish line and start looking at the starting gate.

[CAS]

I'm sorry but if you don't have the finsih gate in sight then the start gate won't happen. you need the end gate to have a goal of what you want to achive or all you doing is piss furting around without getting any where at all

[tomsonite]

... You are arguing semantics. When I said 'adult neurons', I was being general, as this is an online board of non-specialists...

Semantics are important if the SCI community is going to educate itself enough to take well-educated positions when advocating for curative research. That's why I'm making such a big deal about this.

The neurons in the brain & spinal cord that make up the spinal cord tracts do not regenerate... I don't care if neurons with peripheral nerves regenerate and they have a nucleus in the spinal cord...The fact that they regenerate doesn't prove one way or another if environment vs intrinsic capacity is the bigger cause for why spinal cord axons don't regenerate.

It doesn't prove anything, sure, but does that really make them irrelevant? I don't think so. There is much to learn about from how the peripheral nervous system regenerates.

Well how do you define robust? Compared to a control (basically 0 axons) or compared to the total number of propriospinal axons?

If function is restored, the regeneration is robust. Many high functioning incompletes have visual chunks of their spinal cord missing. You don't need 100% of your axons to be very high functioning. I don't think most animals would care about what the image of their spinal cord looks like if they can take a piss.

...Nor is there any concrete proof of recovery of function...

Are you really looking for concrete proof of anything when reading scientific literature?

...then 'Some' axons can regenerate. Which of course means nothing.

Having just one function back vs. no functions back means nothing? I have been told differently.

My opinion is based on scientists who are looking into Gene therapy to cure SCI. Especially from Dr. Murray Blackmore. In fact my next point is taken straight from him. Embryonic neurons can grow axons even in a hostile SCI environment. For example, embryonic neurons implanted into 14 day complete SCI were able to grow axons far and in great amount (visually) through a hostile SCI. Here is an excerpt from Mark Tuszynski's 2012 paper: "Long-Distance Growth and Connectivity of Neural Stem Cells After Severe Spinal Cord Injury" :

"Thus, properties intrinsic to early stage neurons can overcome the inhibitory milieu of the injured adult spinal cord to mount remarkable axonal growth resulting in formation of novel relay circuits that significantly improve function."


Here is a beautiful, clear image of axon growth through hostile environment. (it won't let me paste image).

Link --> http://www.ncbi.nlm.nih.gov/pmc/arti...432/figure/F6/

So when Dr. Steward tried to replicate the Neural Stem Cells + Fibrin, he says that the EMBRYONIC neurons extended axons very far & plentiful inside a hostile SCI environment. But NOT the adult host neurons.
...

Murray Blackmore is someone I have heard talk extensively about how hard it is to regenerate the corticospinal tract - more so than any other tract. That is one of the reasons the corticospinal tract is his main goal.
The link you posted does show pretty significant regeneration. In the full paper, they talk about significant functional recovery, which now forces me to play devil's advocate - do you see any solid concrete proof of recovery of function in this article? Or is all you take from it the axonal regeneration?
It is perfectly plausible that the embryonic neurons could extend their axons far, especially if pushed along by fibrin. I should point out that I haven't ever said that adult neurons are capable of regenerating just as well as they would be at any other point in their life cycle. It is perfectly plausible that embryonic neurons extend axons better then adult neurons since they are genetically pre-dispositioned to. But that doesn't mean the environment is a less significant factor. How would the embryonic neurons have fared without fibrin? How would the adult neurons have fared if we were capable of more significantly re-engineering the injury site and given the animals neuromodulatory therapies?

I hear a lot of talk about scar being a barrier. Ok. Chase or Dr. Silver’s peptide breaks down that barrier (so they say). No robust regeneration. I hear about a lack of a bridge being a barrier. So there have been scaffolds and nerve grafts. Yet I have seen no robust regeneration of host axons. I fully understand that the environment is more complex than that. Yet with neural stem cells and fibrin, I see robust axon growth through a hostile spinal cord environment but only from embryonic stem cells. So fibrin + other non-neuronal neural stem cells (added environment) is a good enough environment for embryonic neurons but not host adult neurons. This leads me to have the OPINION that the intrinsic factors that prevent axon growth of adult host spinal tracts are stronger (not the only) factors than a hostile environment. By a lot.

Again, your opinion is that the regeneration isn't robust - I see return of function and would imagine that is "robust", given what people with SCI have told me. While your argument is a sound one, you must acknowledge that it was embryonic stem cells + fibrin + non-neuronal stem cells, which are a change to the CNS environment. It could be that those factors react better with embryonic neuronal stem cells than adult cells. Are there any studies showing robust (by your definition) regeneration of spinal cord axons with embryonic neural stem cells alone, and no other additions/changes to the environment?

So what is your opinion based on? Just that peripheral nerves regenerate?

I'll reiterate in case I actually have made it that difficult to extrapolate what my opinion is based on from what I've already written. Remember the argument I'm trying to make is that some adult neurons can regenerate their axons, and that the environment of the entire CNS (not just of an SCI) is a VERY significant barrier to axonal regeneration:
-Neurons in the CNS can regenerate their axons that are in the PNS
-There are many more kinds of glia in the CNS that make axonal regeneration much more complicated than in the PNS
-We have evidence of axonal regeneration that has led to functional restoration in mammals without genetic re-engineering
-There are many proteins and growth factors that are found in different quantities between the CNS and PNS, and some are found in the PNS that are not found at all in the CNS (PCAF, as I already mentioned).
-In Murray Blackmore's presentations at W2W, he has talked about how despite successfully changing the genetic make-up of some neurons in the animal brain, significant function has not been restored (I'm not sure how much axonal regeneration there was, but if it doesn't lead to functional restoration, it's pointless).

I'm not saying that all we have to do is create a better environment in the CNS and everything will be peachy. I'm not discounting that gene therapy could absolutely have its place and play a significant role. But it seems to me that we can't discount that the adult central nervous system alone just doesn't seem to be built for axonal regeneration, and that's a big piece of the puzzle we still need to figure out. There are a lot of questions to answer before we can say definitively whether intrinsic regenerative properties or the environment is definitely the biggest factor.