Life on Wheels (75 page)

The brain and spinal cord make up the CNS. The peripheral nervous system (PNS) carries motor impulse messages from the CNS to our muscles and sensory messages to the spinal cord, which carries them back to the brain.

When injured, the PNS recovers, the CNS does not. Why the difference? The PNS and CNS systems are distinguished by two essential qualities.

A different biochemical makeup. The PNS has a biologic environment that supports the process of regeneration, whereas the CNS doesn’t have the right biochemistry for growth. The CNS has been found to contain factors that actually inhibit regeneration.

A different physical structure. Peripheral nerves have a system of sheaths that help direct a damaged nerve back to its “connection” as it regenerates. Central nerves have no such guiding channels. The small amount of regrowth that does occur after an injury has no idea where to go.

To understand the challenge of the immensely intricate research puzzle, we must know something about the way the spinal cord is built. Simplistically, it consists of long nerve axons surrounded by a protective coating called myelin. We need to know what happens to this system when it is injured and what would stimulate growth in a way that will restore function.

The spinal cord is composed of millions of fine nerve fibers called axons, which carry motor impulses to neurons that in turn pass the information to the peripheral nerves and onward to muscles. Sensory messages move in the opposite direction, from nerve endings throughout the body, through the cord, and back to the brain. These nerves are like telephone cables—dense bunches of thin “wires” down which electrical signals travel (Figure 6-1).

The spinal cord itself is made of up of gray matter, which carries both motor and sensory signals, and white matter, made up of myelinated nerves that carry signals from the gray matter between neurons. The spinal cord itself is made up of mostly long axons, which carry signals down to “cell bodies,” which transfer these signals to and from the neurons that communicate with muscles and the body’s largest organ—the skin and its sensory nerves.

Sometimes, in response to trauma, the body does manage to accomplish a degree of axonal regrowth on its own. Small amounts of nerve repair and remyelination have been observed. Central nerves have been known to sprout, sending out new shoots looking for a connection, but the odds are not good of linking up to a useful receptor without some help. The body really can’t do this repair by itself.

As soon as a spinal cord is injured, a complex chain of events begins. The cord starts to hemorrhage, bleeding from the inside out. The cord—a soft, gelatinous material—is denied the basic nutrients and fuel it needs to function and maintain itself. The contents of the nerve, its axoplasm, leak out the end, immediately shortening the broken end of the nerve and putting distance between it and its former connection. The portion of the axon that is away from the neuronal cell body dies, while the cell body and remainder of its axon survive.

Soon after trauma, the body attempts to clean up the mess in a chemical onslaught that causes further secondary damage. As Melinda Kelley, PhD, former Associate Director of Research at the Paralyzed Veterans of America, describes it:

As damaged cells get digested by the body, some healthy ones get eaten too, spreading the extent of the injury. The body tries vainly to repair itself but, in reality, causes more harm.

The body has an intelligence of its own, a miraculous system of programmed responses to its own conditions. One such process called apoptosis is a sort of cell suicide. When cells discover they are no longer needed by the body, they destroy themselves. Spinal cord and brain trauma trick cells into believing they have completed their work and apoptosis begins, further increasing the degree of secondary damage. Spinal cord researcher Dennis Choi, MD, PhD, of Washington University in St. Louis has been addressing the question of apoptosis:

Within a week, nerve cells begin to degenerate, and whatever regenerative efforts the body had been trying come to a stop. Following injury, the glial scar—a physical and chemical barrier—forms, which obstructs neuronal growth. It is a chemical barrier due to growth inhibitors. The issue of glial scarring has been controversial, but current science appears to recognize it as a meaningful factor in the CNS injury puzzle.

Axons are surrounded by a protective material called myelin. When an axon is damaged and retreats, the myelin that surrounds it is also affected. As described by Dr. Wise Young of the W.M. Keck Center for Collaborative Neuroscience at Rutgers, the State University of New Jersey:

Remyelination is a substantial part of the spinal cord cure puzzle, since a regenerated axon will not work without a restored myelin layer to protect it. In an incomplete SCI, it is not unusual for some axons to remain intact, yet be unable to pass impulses because of disruptions to their myelin. Nerve regrowth may not be the entire challenge here. Restoring myelin could mean a degree of renewed function for some spinal cord-injured persons. The majority of SCIs are incomplete injuries.

The degree of axonal death just after the injury is further exacerbated by a loss of circulation to the area. Blood supply through a system of very fine, microscopic capillaries is disrupted. Traumatized tissues are damaged by this loss of blood, but so are nearby healthy nerve tissues that have not been directly impacted but, nonetheless, need a constant supply of nutrients.

Blood and all of its nutrients and factors must be present to foster regeneration. For a true recovery, a permanent vascular system must be reestablished. This extremely delicate network of capillaries must integrate with existing tissues and maintain the flow of metabolic materials into and out of the new tissues.

The first successes in axonal regeneration—although exciting—produced disappointingly small amounts of growth. Recent efforts have been more encouraging in getting axons to grow over longer distances and are beginning to produce promising functional improvement.

The PNS has Schwann cells that promote growth and remyelination, but these are not present in the CNS. The central system has cells called oligodendrocytes, which produce myelin; however, they are unable to produce enough to compensate for the degree of damage involved here.

There are just not enough nerve growth factors present in the CNS to respond to trauma. The body apparently has figured that, once born, it no longer needs the capacity to grow central nerve tissue. Even worse, there are “inhibitors” that have been identified as getting in the way of the body’s attempt to regenerate.

But there’s more. Getting a nerve to grow with proper insulation is useless unless the nerve can get to the right destination. Remember that the CNS doesn’t have the guiding channels found in the peripheral system. The axon has to reach the correct location. In animal studies, there have been cases of regeneration with no functional improvement whatsoever.

But it is not clear that specific nerves must make exact connections. The body might be able to retrain itself to use new connections, in whatever manner it needs to proceed. The receptor sites needing an axonal path to the brain might also have the ability reach out and grab a new axon, rather than having to guide an axon to the site itself. All of this is very preliminary.

In some cases, the spinal cord becomes attached to surrounding tissues. This is known as tethering and can restrict the flow of spinal fluids— which surround the cord—past the injury site. Pain and loss of function can result.

Surgery to untether the spinal cord is already being performed. Of 40 people operated on at the University of Miami and whose outcomes were reported by the Miami Project to Cure Paralysis, 79% showed improved motor function, and 62% had reduction in chronic pain.
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For some people, untethering surgery might be necessary as part of a spinal cord regeneration therapy.

Suppose we get axons to grow—possibly as many as five million are needed—by supplying the growth factors and obstructing the inhibitors. We ensure that they are protected by myelin. We provide a continuing supply of blood and nutrients to the area and get the scarring out of the way to allow growth. We get the axonal end to grow long enough and direct it to the right location—or train the body to reroute its messages—and form working neurons and synapses to get the message out to the muscles. Can we walk now?

That depends. Now we need to ask to what degree atrophied muscles have the capacity to receive impulses and start to produce muscle fiber capable of sufficient contraction. In other words, will the muscles work, and how strong can they become? To carry the weight of the upper body and to work continuously without early fatigue is a tall order. After only months of atrophy from disuse, the degree of lost muscle strength is considerable. After years of disuse, who knows?

Whether muscles can work again depends on whether or not there is damage to “lower motor neurons,” a particular type of cell in the nervous system that carries messages directly to muscles. Even if the brain-to-muscle communication is interrupted, the muscles can still be receiving enough signal for muscle cells to be maintained. Without lower motor neuron signals, muscle cells die. Ironically, spasticity (often seen as a disadvantage) preserves considerable muscle tone. People with spasticity will have less work to do rebuilding muscle if the cord is regenerated. There is also no question that spastic muscles have functioning motor neurons.

Many people with neurologic conditions develop contractures, in which muscles, tendons, and ligaments are permanently shortened. Even if the spinal cord can be completely cured, there are considerable issues of rehabilitation involved in getting someone into the right posture, building muscle, and re-teaching them the process of walking. Once the nervous system gets talking again, there is a major process of rehabilitation left to face.