Leif,

Somewhere along the line, you seem to have gotten the impression that the spinal cord circuitry is very complicated and that we must reproduce the complexity in its entirety before there would be substantial funcitonal return. I have indicated that I believe otherwise. You ask for evidence. Fair enough. Let me try.

Many complex functions are programed in the spinal cord and one needs relatively few descending axons to activate and control these functions. For example, standing/balancing, walking/trotting/running/pivoting, micturition, ejaculation, farting, passing stools, and other functions can occur with little or no control from the brain. These programs reside in the spinal cord and do not require the brain. For example, a beheaded chicken can run quite well around the courtyard (usually in circles because it is blind). Passing of stools, in fact, is probably not programmed in the spinal cord but in the mesenteric ganglia that coordinate gut movement. Most people with "complete" spinal cord injury can pass gas through their anus, a complex act that requires detection of gas in rectum and the sphincter will close if solid stool passes into the rectum. One probably requires less than 10% of the descending pathways of the spinal cord to initiate these functions. It is the reason why people with even severe injuries with some partial preservation of motor or sensory function will recover most of these functions. Most people have preservation of some pathways across the injury site. One needs only to regenerate a small percentage of axons to add to the surviving axons in order to have substantial return of function.

The spinal cord is much more plastic that we realize and that plasticity does not require the brain. For example, if you take a cat and transect its spinal cord, that cat is initially unable to walk but can be trained to walk on a treadmill if its weight is supported. This training is most effective in young animals but most importantly the behavior is malleable by noxious stimulation and other sensory input. For example, if you put something to trip the legs of a cat with transected spinal cord walking on treadmill, the legs will change their stride length to avoid the tripping or to avoid falling from the tripping when stimulated. Likewise, if you apply noxious stimulation to the feet, this will cause lasting disruption of the walking behavior.

Many investigators have shown that the spinal cord is capable of learning and remembering. In fact, many laboratories have now shown that spinal cord below a transection is capable of learning from both operant and associative conditioning. For it is possible to train an animal to change its monosynaptic reflex excitability in response to certain stimulation and show that the spinal cord will retain this learned behavior for long periods of time. Some of this experience suggests that we need to be careful with locomotor training methods because some types of stimuli (such as functional electrical stimulation) may be disruptive of behavior.

So, there is much evidence to suggest that the spinal cord is "intelligent" and is capable of substantial function and even learning without control by the brain. Relatively few descending axons and necessary and sufficient to control many of the functions in the spinal cord. This is both good and bad news. The good news is that we do not need to regenerate many axons to get functional return. The bad news is that if there is injury to the gray matter circuitry below the injury site, functional recovery may be limited even if we were able to regenerate long fiber tract.

The above is one of the reasons why we are limiting the injury levels to T10. The reason is that at the spinal cord ends at the L1 vertebral segment and injuries with neurological levels of T11 or lower frequently involve the thoracolumbar cord where spinal cord centers for walking (central pattern generator) and micturition (onuf's nucleus) are located. At this point, some people might conclude that these spinal cord centers, once damaged, would be difficult to replace. However, here again, I think that there is reason to believe that the system is quite plastic and let me give you an example of the plasticity of the system that allows amazing recovery of certain function.

The example that gives me much hope is the work of Xiao who has been doing peripheral nerve bridging from lumbar roots (such as L2) to sacral roots (S2) to restore micturition in human. As many here know, I have talked about the work of Xiao, et al. who has taken ventral roots below the injury site to connect ot the pudendal nerve, which innervate the bladder and sphincters. Xiao has shown that, after these predominantly somatic roots will innervate the bladder, sensory stimulation of the dermatomes for the segments from which the donor roots are obtained can activate micturition. He has shown pictures of people who scratch a dermatome and then would have a three-foot stream of urine.

The above is an amazing result for following reasons. First, the donor roots (i.e. L2) normally innervate somatic muscle, i.e. predominantly cholinergic. The pudendal nerve clearly innervate a variety of target tissues, from smooth muscle to striated muscle. The innervation of the bladder and its sphincters are sympathetic and parasympathetic, i.e. catecholaminergic and cholinergic. Yet, the ventral roots from somatic segments of the spinal cord can adapt to produce a full micturition response from the bladder. Second, Xiao reports that children with incomplete spinal cord injury or spina bifida actually learn to control micturition voluntarily after such ventral root bridge and may no loner require stimulation of the dermatome. Third, the system clearly is using other or its original sensory input than the bridged roots, the ventral roots are used to bridge to the pudendal nerve (end-to-side).

The above indicate that the spinal cord may have ways of reorganizing that are quite unexpected and poorly understood. I think that as we study the reorganization of the spinal cord, we will find many surprising capabilities of the spinal cord to adapt to losses, not only for the long tracts but also losses of gray matter centers. One likely possibility is that the spinal cord is not only redundant regarding long tracts but also very redundant and plastic when it comes to gray matter centers. We have a lot of learn yet about the spinal cord but I don't think that this should stop us from starting the clinical trials and seeing what works and what does not work.

Observations of human recovery is teaching us a lot about the capabilities of th spinal cord. Many of these capabilities are surprising and not predictable based on our current understanding of spinal cord anatomy and circuitry. My good friend Milan Dimitrijevic once pointed out that the injured spinal cord is a "new" spinal cord. It no longer follows the rules of anatomy as we understand it. It has changed in order to maximize function. We need to understand these changes and how to maximize and enhance these changes. In the end, I think that this will be a very fruitful area of research. We have a lot of research yet to do, particularly to understand how stem cells and newly created neurons may interact with this "new" spinal cord.

Wise.