On Memorial Day weekend in 1995, in a devastating accident, an
experienced rider was thrown head first from his horse during a
jumping competition in Culpeper County, Virginia. He fractured
the first two vertebrae in his neck and crushed his spinal cord
just as it exits from the skull.
The 42-year-old man received emergency resuscitation, which saved his life, but he lost sensation in most of his body and the ability to move his arms, legs, and torso. The rider, of course, was actor Christopher Reeve, who has since become a prominent advocate for more research on spinal cord regeneration.
When Reeve was injured, he received state-of-the art medical care, including methylprednisolone. Scientists had studied this steroid drug for years before they learned that it can sometimes prevent complications associated with spinal cord injury if given immediately after the trauma occurs. Although the damage to Reeve's spinal cord was severe, he has regained some of the function of his spinal nerves just below the site of injury. He and thousands of other people with spinal cord injuries now await new treatments that will at least lessen the severity of their paralysis.
Today, much of the excitement -- and many of the
questions -- about repairing damaged tissue in the brain or
spinal cord focuses on coaxing injured nerve cells to regenerate
and recover their lost functions. Some researchers believe it may
be necessary to replace entire nerve cells that have died, after
the brain is damaged by head trauma or by degenerative diseases
such as Parkinson's. But in spinal cord injuries, nerve cell
bodies usually survive. So researchers seek ways to regrow
damaged axons, the thin fibers that extend from
nerve cell bodies and signal the next nerve cell to respond.
[Click HERE for story on head trauma]
Triggering spinal cord axons to regrow is not a simple matter, however. The axons travel in bundles or pathways up and down the cord, and each pathway carries different kinds of information. The downward or descending pathways from the brain to the spinal cord control a person's deliberate or voluntary movements. The upward or ascending pathways from the spinal cord to the brain carry sensory information about touch, pain, temperature, and body position. Thus, spinal cord injuries that damage both the descending and ascending pathways affect a person's ability to move and to feel sensation.
But even if researchers can stimulate injured spinal cord axons to regrow up and down the spinal cord, the problem may not be fixed. "Axons need to do more than grow," says Wise Young, a neurologist and research scientist in the department of neurosurgery at New York University Medical Center in New York City. "They also need to attach to their target cells." The point at which the endings of a nerve cell axon contact the next cell is not a physical attachment, however. Instead, a nerve cell communicates with its target cell across a small gap called a synapse. The ideal treatment for spinal cord injury would stimulate both axon regeneration and the formation of functional synapses with the right target cells. And in humans, that combination of achievements has eluded researchers.
Nevertheless,
says Young, recent experiments with adult rats show that some
axon regeneration and recovery after severe spinal cord injury
might be possible. Although the experiments leave some questions
unanswered and it will be important for other groups of
researchers to repeat the study, they have generated enormous
interest.
"We have been doing this sort of experiment for the past 25 years, but it is only now that something has come out of it," says Lars Olson, {Link to "Swedish Researchers Combine Treatments To Repair Severed Rat Spinal Cords" } a physician and research scientist at the Karolinska Institute in Stockholm, Sweden, who heads the research team that reported the new results. In their experiments, Henrich Cheng, the surgeon in Olson's group, cut through the spinal cords of adult rats, removed a short segment from each, and grafted into the gap a 'bridge' of 18 tiny pieces of nerve taken from the muscle tissue between the animal's ribs. Cheng added to the graft a mixture of biological 'glue' that contained fibrin (a blood-clotting protein) and a chemical that enhances the outgrowth of fibers from the severed spinal cord axons. After six months, a small number of the spinal cord axons had grown through the graft and the treated animals had regained some ability to move their hind limbs (1).
Newspapers and TV stations reported the new findings with great excitement. "Doctors in Sweden Document That a Severed Spinal Cord Can Repair Itself," read a headline in The New York Times on July 26, 1996. Had Olson and his collaborators done what no other scientists had been able to do?
A panel of neuroscientists who spoke at the annual meeting of the Society for Neuroscience in November, 1996, viewed the Swedish study more cautiously. "The study needs to be replicated independently in another laboratory," says Fred Gage, a neuroscientist at the University of California at San Diego in La Jolla and a member of the panel. Gage agrees that the severed spinal cord axons regrew in the rats. But he is not convinced that those newly formed fibers actually caused the animals' partial recovery of their ability to walk, an issue that he believes can be resolved by more experiments.
Such differences of opinion are not unusual among scientists. Researchers who study spinal cord regeneration approach the problem from many perspectives, and it is inevitable -- and important --that they challenge each other's findings.
In fact, studies of spinal cord regeneration have a long history and embrace many different research strategies. Some scientists want to understand a century-old observation: In a mature mammal, why don't the brain and spinal cord -- which together form the central nervous system (CNS) -- repair themselves following injury or disease? Injured nerve pathways in the adult peripheral nervous system (PNS), which supplies the rest of the body, are often capable of regrowth and recovery. So why doesn't the adult CNS have the same ability? (See: "Why Don't the Brain and Spinal Cord Repair Themselves?")
Other scientists ask why the CNS of a very young mammal can repair itself automatically but the CNS of an adult mammal cannot. Much of their research focuses on the differences between the cellular and molecular environments of the still-developing brain and spinal cord, and those of the adult CNS. For instance, how do the populations of cells differ in the embryonic and mature CNS? What combinations of nourishing proteins, called neurotrophic factors, might very young CNS cells produce that corresponding adult tissues may lack? What protein factors in the adult central nervous system inhibit rather than encourage growth? And how does the extracellular matrix, the noncellular material that lies outside nerve cells, differ in the developing and adult central nervous systems? As scientists learn the answers to these and other questions about the development and function of the central nervous system, they can design strategies for repairing damage to the spinal cord and brain.
Researchers all over the world are trying to find treatments for people who have CNS injuries. Most of them believe that a combination of therapies rather than a single treatment will be necessary, and many teams of scientists are testing experimental treatments in laboratory animals. When will new treatments be ready to test in people?
"I've been asked this question many times," says Young. In fact, Christopher Reeve wanted to know. "I told him that it takes about seven years for any therapy being tested in animal studies to reach humans," says Young. "So Reeve has set a seven-year goal. Seven years has become a rallying cry for research on spinal cord regeneration." The seven years will be up when Reeve turns 50.
Additional Reading:
1. H. Cheng, Y. Cao, and L. Olson. "Spinal cord repair in adult paraplegic rats: Partial restoration of hind limb function." Science 273: 510-513 (1996).
2. W. Young. "Spinal cord regeneration." Science 273: 451 (1996).
3. M. E. Schwab and D. Bartholdi. "Degeneration and regeneration of axons in the lesioned spinal cord." Physiol. Rev. 76 (2): 319-370 (1996).
