SCI Forum Reports
Recovery Research
January 7, 1997
"The human spinal cord is about as big (around) as your little finger, and yet the structure is very complex," said James Little, MD , an associate professor of rehabilitation medicine affiliated with the Seattle Veterans Affairs Medical Center. "There are perhaps 10 million nerve cells in the human spinal cord, and a billion connections between all those different nerve cells."
Every inch or so along the length of the spinal cord, bundles of nerves exit the cord and branch out into the body to provide motor control and receive sensory input. Nerves that exit the cord in the neck (cervical region) provide sensation and movement to the arms, while those in the lower back (lumbosacral region) go to the legs. Nerves that control the bowels and bladder exit from the lowest part of the cord (sacral region).
"There's a ring of bone at each of these levels that surrounds the spinal cord and protects it," Little said. The nerve bundles exiting the cord are numbered from the brain downward, so the sixth bundle from the top, which is in the cervical region, is known as "C6". If someone is a C6 tetraplegic, his or her cord injury is just below the C6 bundle, leaving function intact from the C6 level upward.
There are two types of nerve cells in the spinal cord. Upper motor neurons have cell bodies located in the brain and extend long branches, called axons, down through the spinal cord. In the cord, the axons make contact with lower motor neurons, which have their cell bodies in the spinal cord and extend axons out to the body.
"We often think of the way the spinal cord works in terms of upper motor neurons, which connect the brain to the spinal cord, and lower motor neurons, which connect the spinal cord to the muscle," Little said.Spinal cord injuries can affect either type of neuron, and most often affect both. Upper motor neuron deficits are usually more disabling, because they affect all function below the level of the injury, while lower motor neuron deficits usually affect only the specific areas served by the damaged nerve.
Most nerve cells make hundreds or thousands of connections with other nerve cells via junctions called synapses at the ends of the axons. The axons are coated with insulation, called myelin, which greatly improves their ability to conduct electric signals. Severe injuries can cause the axons to die, while less severe injuries may leave the axons intact but damage their myelin coating, blocking the ability to conduct signals. Injuries can also be complete, affecting all of the axons in the spinal cord, or incomplete, affecting some axons and not others.
Many people with SCI experience some natural recovery of function after their injuries. "Someone may start out with a C5-level injury, and then regain some C6-level function or sensation," Little said. "We have treatments that help enhance this recovery." During the acute phase, these treatments include surgery to stabilize the spine and/or relieve pressure on the spinal cord, and medications, such as methylprednisolone, a steroid that reduces swelling and stabilizes nerve membranes. After the acute period, there is evidence that rehabilitation activities and treatment of spasticity can help enhance recovery.
In the search for ways to further improve recovery, most current research is focusing on one of three areas: 1) enhancing function of damaged myelin, 2) encouraging spared axons to grow new synapses and take over the functions of damaged axons, and 3) helping damaged axons to regenerate. Upper motor neuron regeneration is receiving the most attention, Little said, because if achieved it would offer the best hope for recovery to people with SCI.
In lower vertebrates, such as fish, axons in the spinal cord will grow back after injury, but in mammals this growth is severely limited. However, Little said, "there's more hope now that this may be a solvable problem."
In a study on cats in the early 1980s, animal researchers attached pieces of peripheral nerve, taken from the leg, to two places on the spinal cord to see if the peripheral nerve would act as a "bridge" through which spinal axons could grow. After several months, they found that spinal axons had grown 3-4 cm inside the nerve bridge. "This renewed people's hope," Little said. "Three or four centimeters is plenty long to get past most spinal cord injuries." Unfortunately, the growing axons failed to make functional connections once they got back into the spinal cord.
Last summer, researchers in Sweden published the results of an experiment in which they microscopically grafted 18 peripheral nerve bridges into the severed spinal cords of rats. Their goal was to guide growing axons to locations where they might make useful connections, and the rats did experience some functional improvement, Little said.
"This does suggest that you can get neurons to grow, and you can get functional connections. Are we 'there' yet? No. There are still some big hurdles that have to be overcome. It's going to be tougher in people than in rats."
Meanwhile, trials of a new drug, 4-amino-pyridine (4-AP), are scheduled to begin this year in the United States. This drug may be able to restore conduction in some axons that have damaged myelin due to SCI. Fetal neuron grafts are being explored intensively in animal studies, but so far the functional gains produced have been "pretty modest," Little said.
Meanwhile, he offered a list of things that individuals with SCI can do to prepare for future breakthroughs. The first priority, he said, is to protect your yealth -- maintain your range of motion and protect your skin from breakdown. Little also recommends supporting SCI research, both politically and by participating in research studies (but only after carefully considering any risks involved).
People with SCI should stay aware of new developments, yet they should also be skeptical. "There have been a lot of treatments tried, and many of them have not panned out," Little said. "You need to be cautious, and scrutinize any claims." Before a new technique is tried in humans, there should be some published results from animal studies indicating that the technique has been successful. If a technique is being offered on a clinical basis to humans, there should be some published data indicating success in human subjects as well as animals. It's also a good sign if the technique is being used by more than one center.
"As far as regenerating the human spinal cord, the fundamental breakthroughs are going to have to come through animal work and basic science," Little said.