Jumping or bridging the damaged area

[bigbob]

I have always compared the nervous system to an electric circuit or more closely to that of a computer. In the beginning you had to set all kinds of dip switches and jumpers. Now the motherboard knows exactly what cpu is installed and sets the proper freq. and voltage. Would it be possible to do this in the nervous system? Example- a unit could be installed before the break or damage that could read all the signals, or the outputs. On the other side of the break a similiar unit could monitor the paths of the nerves to the muscles. Once it is configured would it be possible to assign which signal would go to which nerve, after the break. Kinda like a smart relay system.

[Wise Young]

Bigbob,

There is a danger to equating the nervous system to an electronic circuit because it leads to all sorts of misleading conclusions. Here are some big differences:

A single neuron is in many ways a cpu. Each neuron has memory and programming and hence is like a small computer. It is also self-programming and almost all neuronal circuits have feedback circuits. A neuron may receive hundreds of parallel inputs, but a neuron usually has a serial output that is in turn connected to multiple neurons serially. While the output of a neuron is digital (action potential) and mostly serial, it often behaves like an analog processor, i.e. it sums and integrates the signals from many synergistic and competing sources.
Neurons cannot reroute signals. To do so, they have to disconnect and reconnect.

This is just the beginning. I will add more.

Wise.

[bigbob]

Sounds more complicated then I thought, I thought each path was dedicated to a certain function. I did not realize that there are series and parallel connections.But then the computer also controls many inputs and outputs and many different functions. My thinking was that the cells are okay before the injury, and unless there is a breakdown of the nerves after injury, I would think they could still be used to transmitt information. I thought inputing signals to a processor right before the damaged area that was wired to another processor after the injury and directly connected to the nerves might be a way of approach. Like signals we send to a satelite and then send them back to earth. In the case of sci it would be like a wired remote control, but buttons wouldn't have to be pushed as the remote control would get its assignment from the spinal cord before the injury. I'm just thinking out loud and hope that maybe something I say could be a catalyst for a improved version of what I am trying to say. Sometimes great ideas come from simple minds. And then a scientist with the know how could redesign and improve those thoughts. I guess my main idea was that maybe there is a way to bypass the injury, instead of trying to fix it. Wise- thanks for your reply and putting my post in the right topic area. I look foward to reading more on this subject, as you said you will follow up in your reply

[etexley]

Bigbob,

It's sort of like cutting and trying to reconnect a fiberoptic cable. You're not going to be able to connect ever strand on top to the strands on the bottom, you know?

The good part about the cord is that it is ...meaning that the responsiblities of connections can change. I have an idea that this is why an incomplete injury has so much room to recover. And it's VERY redundant...there are many connections which are responsible for innervating the same peripheral nerves.

My understanding is that the majority of the axons in the cord are "inhibitory" meaning that they inhibit spasms. Lately I'm beginning to find value in trying to make my leg spasms voluntary...if I can start and stop a leg spasm at will, it's voluntary control of my leg muscles, isn't it?

[Wise Young]

The most prevalent cause of recovery probably is sprouting of surviving axons. As many of you know, if you cut half of the spinal cord (hemisection), most animals and people will recover bilateral locomotion. Rats, for example, will recover walking on both legs within 2 weeks after a hemisection of the spinal cord.

Several years ago, we studied this in rats and applied a serotonin antagonist called mianserin. What we found was that blockade of serotonin reduces locomotor ability of hemisected rats. More interestingly, we found that serotonergic fibers that remain on one side of the spinal cord sprout below the injury site and cross the midline to connect to the other side. The timing and degree of sprouting correlated with recovery of bilateral locomotion.

Many people have studied the minimum necessary number of axons that are required for walking recovery. In the early 1950's, Windle, et al. showed that cats can recover walking even if they cut 90% of the spinal cord. Blight, et al. in the 1980's counted axons and found that many cats are indeed able to walk if they have 10% of their axons remaining. Finally, the recent work of You, et al. (2003) suggests that 5% of the axons in the ventral part of the spinal cord is sufficient to support locomotor recovery.

Wise.

• Saruhashi Y and Young W (1994). Effect of mianserin on locomotory function after thoracic spinal cord hemisection in rats. Exp Neurol 129:207-16. Summary: To study the role of serotonin (5-HT) in spinal cord injury, we observed the effects of mianserin (a 5-HT1c and 5-HT2 receptor antagonist) on rat locomotory function after thoracic spinal cord hemisection. Three groups of rats were studied: sham, A, and B. The sham group (n = 4) received laminectomy and a 3-day course of mianserin (5 mg/kg ip); group A (n = 12) had laminectomy, hemisection, and weekly 3-day courses of saline or mianserin; group B (n = 12) was identical to group A except that the rats received saline. The rats were evaluated every other day for 6 weeks using a 0-14 point scale. Hemisection markedly reduced mean ipsilateral hindlimb scores from 14.0 to 4.0 +/- 0.4 and 4.6 +/- 0.2 (mean +/- standard deviation) in groups A and B, respectively. The saline-treated rats recovered to scores of 9 or 10 by Day 7, 12 or 13 by Day 14, and normal by Day 21. Mianserin significantly but transiently depressed mean locomotory scores, from 12.1 +/- 0.6 to 10.0 +/- 0.4 (P < 0.05, Mann-Whitney U test) in the second week and from 14.0 +/- 0.0 to 12.1 +/- 0.6 [P < 0.05, Mann-Whitney U test) in the fourth week after hemisection. Locomotory scores of mianserin-treated rats did not differ significantly from control saline-treated rats by 7 days after treatment. Immunohistological studies of the spinal cords revealed a marked reduction of 5-HT-containing terminals in ipsilateral but not contralateral lumbosacral cord by 2 weeks after hemisection. By 4 weeks after hemisection, 5-HT-immunoreactive fibers and terminals partly returned to the ipsilateral lumbosacral cord, corresponding temporally with locomotory recovery. Thus, 5-HT may play a role in recovery after hemisection. Anti-serotonergic drugs should be cautiously administered to patients recovering from spinal cord injury. Department of Neurosurgery, New York University Medical Center, New York 10016.

• Saruhashi Y, Young W and Perkins R (1996). The recovery of 5-HT immunoreactivity in lumbosacral spinal cord and locomotor function after thoracic hemisection. Exp Neurol 139:203-13. Summary: To determine the role of serotonin (5-HT) in recovery from spinal cord injury, we examined spinal cord 5-HT immunohistologically and assessed locomotor recovery after thoracic (T8) spinal cord hemisection in 68 rats. Forty eight rats had laminectomy and hemisection, while the remaining 20 rats received laminectomy only. All rats were evaluated every other day for 4 weeks, using a 0-14 point scale open field test. Hemisection markedly reduced mean hindlimbs scores from 14 to 1.5 +/- 0.32 and 5.6 +/- 0.31 (mean +/- standard error of mean) in the ipsilateral and contralateral side, respectively. The rats all recovered apparently normal walking by 4 weeks. The 5-HT immunohistological study revealed a marked reduction of 5-HT-containing terminals in the ipsilateral but not the contralateral lumbosacral cord by 1 week after hemisection. By 4 weeks after hemisection, 5-HT immunoreactive fibers and terminals returned to the ipsilateral lumbosacral cord, with many 5-HT fibers crossing over the central canal at thoracic level. We estimated the recovery of 5-HT neural elements in lumbosacral ventral horn by ranking 5-HT staining intensity and counting 5-HT terminals. The return of 5-HT immunoreactivity of the lumbosacral ventral horn correlated with locomotor recovery. Locomotory recovery invariably occurred when the density of 5-HT terminals approached 20% of control values. These results indicate that return of 5-HT fibers and terminals predict the time course and extent of locomotory recovery after thoracic spinal cord hemisection. Department of Neurosurgery, New York University Medical Center, New York 10016, USA.

• Windle WF, Smart JO and Beers JJ (1958). Residual function after subtotal spinal cord transection in adult cats. Neurology 8:518-521. Summary:

• Puchala E and Windle WF (1977). The possibility of structural and functional restitution after spinal cord injury. A review. Exp Neurol 55:1-42. Summary:

• Blight AR and DeCrescito V (1986). Morphometric analysis of experimental spinal cord injury in the cat: the relation of injury intensity to survival of myelinated axons. Neuroscience 19:321-341. Summary: The pattern of axonal destruction and demyelination that occurs in experimental contusion injury of cat thoracic spinal cord was studied by line sampling of axons in 1 micron thick plastic sections with the light microscope. Injuries were produced by a weight-drop apparatus, with the vertebral body (T9) below the impact stabilized by supports under the transverse processes. The effects of two combinations of weight and height were examined: 10 or 13 g dropped 20 cm onto an impact area of 5 mm diameter. Animals were kept for 3-5 months after injury, then fixed by perfusion for histological analysis. The number of surviving myelinated axons was found to vary both with the weight used and with the size of the spinal cord. A measure of impact intensity was derived from the calculated momentum of the weight at impact divided by the cross sectional area of the cord (interpolated from dimensions measured rostral and caudal of the lesion following fixation). At impact intensities greater than 0.02 kg-m/s/cm2 there was practically no survival of axons at the center of the injury site, combined with almost complete breakdown of the pial margin. Between 0.08 and 0.2 kg-m/s/cm2 the number of surviving axons varied between 100,000 and 2,000, approximating a negative exponential function (r = -0.88). The number of axons surviving in the outer 100 microns of the cord varied practically linearly (r = -0.82) between near normal and less than 1% of normal over the same range of injury intensity. The number of surviving axons decreased with depth from the pia, also approximating a negative exponential function, with a 10-fold decrease in density over approximately 500 microns. The average slope of this relation with depth remained similar over the range of injury intensity examined, though the slope appeared inversely related to variation in axonal survival for different individuals at a given intensity. It is argued that the loss of axons is probably determined primarily by mechanical stretch at the time of impact. Its centrifugal pattern may be explained by longitudinal displacement of the central contents of the cord, reflecting the viscoelastic "boundary layer" properties of parenchymal flow within the meningeal tube. This is illustrated with reference to the behavior of a gelatin model under compression. The preferential loss of large caliber axons and the characteristic shift to abnormally thin myelin sheaths (resulting from post-traumatic demyelination) both varied in extent independently of injury intensity and overall axonal survival.(ABSTRACT TRUNCATED AT 400 WORDS). Author-abstract.


• You SW, Chen BY, Liu HL, Lang B, Xia JL, Jiao XY and Ju G (2003). Spontaneous recovery of locomotion induced by remaining fibers after spinal cord transection in adult rats. Restor Neurol Neurosci 21:39-45. Summary: PURPOSE: A major issue in analysis of experimental results after spinal cord injury is spontaneous functional recovery induced by remaining nerve fibers. The authors investigated the relationship between the degree of locomotor recovery and the percentage and location of the fibers that spared spinal cord transection. METHODS: The spinal cords of 12 adult rats were transected at T9 with a razor blade, which often resulted in sparing of nerve fibers in the ventral spinal cord. The incompletely-transected animals were used to study the degree of spontaneous recovery of hindlimb locomotion, evaluated with the BBB rating scale, in correlation to the extent and location of the remaining fibers. RESULTS: Incomplete transection was found in the ventral spinal cord in 42% of the animals. The degree of locomotor recovery was highly correlated with the percentage of the remaining fibers in the ventral and ventrolateral funiculi. In one of the rats, 4.82% of remaining fibers in unilateral ventrolateral funiculus were able to sustain a certain recovery of locomotion. CONCLUSIONS: Less than 5% of remaining ventrolateral white matter is sufficient for an unequivocal motor recovery after incomplete spinal cord injury. Therefore, for studies with spinal cord transection, the completeness of sectioning should be carefully checked before any conclusion can be reached. The fact that the degree of locomotor recovery is correlated with the percentage of remaining fibers in the ventrolateral spinal cord, exclusive of most of the descending motor tracts, may imply an essential role of propriospinal connections in the initiation of spontaneous locomotor recovery. Institute of Neurosciences, The Fourth Military Medical University, Xi'an, 710032, China.

[Faye]

"The fact that the degree of locomotor recovery is correlated with the percentage of remaining fibers in the ventrolateral spinal cord, exclusive of most of the descending motor tracts, may imply an essential role of propriospinal connections in the initiation of spontaneous locomotor recovery. Institute of Neurosciences, The Fourth Military Medical University, Xi'an, 710032, China."

Dr. Young,
If this were also the case in humans, wouldn't many more people recover walking ability than is currently the case? Or do we lack the kind of rigorous intense training for say 18 months to accomplish this?

[Wise Young]

Faye, a large majority of people who are "incomplete" do recover walking, including people who have the Brown-Secquard syndrome (hemisection). We have several polls here that indicate that over half of all ASIA B's and C's recover walking. Most of these people have probably lost half or more of the axons in their spinal cord. By the way, millions of people who suffer transient spinal cord injury (these are called "stingers" or "burners") or whiplash injuries where they have pain, numbness, and weakness for several months recover ability to walk.

There is a population of people who were ASIA C during the first few days after injury and who do not recover walking. These are the people who are mostly likely to benefit from intensive ambulation training. Likewise, there is a smaller population of people who are ASIA B who may also benefit from ambulation training.

You are right in that there are relatively few facilities that can provide intensive locomotor therapy and only a small percentage of people with SCI have received intensive locomotor training. Furthermore, only highly motivated people who can afford the time and cost of the training are currently doing it. There is also the question whether earlier training would be more effective than waiting many years and then doing the training.

Wise.

[Wise Young]

Here is a picture of a pyramidal neuron in the cortex, from an original slide made by Santiago Ramon y Cajal who proposed and established the concept of a neuron. The picture below is his drawing of these cortical neurons. http://www.nobel.se/medicine/articles/cajal/#1

http://www.nobel.se/medicine/articles/cajal/6.jpg

http://www.nobel.se/medicine/articles/cajal/10.gif