One injured nerve fiber heals another.

In an unusual finding that suggests a new strategy for healing damaged spinal cords, scientists have shown that severing nerve fibers in the body's periphery stimulates repair of related fibers within the cord. The counterintuitive research tackles the perplexing issue of why peripheral nerve fibers regenerate but those in the central nervous system--the brain and spinal cord--do not.

"The conventional explanation is that the environment of the peripheral nervous system is permissive [to regrowth], whereas in the central nervous system, the environment is hostile," says Clifford J. Woolf of Massachusetts General Hospital in Boston. Indeed, myelin, the insulating sheath around nerve cell fibers, inhibits regrowth in the spinal cord but not in the periphery.

Questioning the importance of environment, Woolf and his colleague Simona Neumann wondered if peripheral nerves simply respond better to damage. When such cells suffer an injury, they switch on many of the same genes employed during their original growth. "Maybe the problem of a lack of growth in the central nervous system is that [damaged] cells don't switch into an actively growing state," suggests Woolf.

The researchers found a perfect test bed for this idea: Some sensory nerve cells extend fibers, or axons, into both the peripheral and central nervous systems. In the cells studied by Woolf's group, the main body sits just outside the spinal cord. The peripheral axon--for example, one in the sciatic nerve running down the leg--reports sensory information. To carry that sensory data to the brain, each cell has a second axon that enters the spinal column and ascends the cord.

In their initial experiment, Neumann and Woolf simultaneously severed the peripheral and central axons of these nerve cells in rats. The peripheral damage stimulated the injured central axons to partially regenerate, they report in the May NEURON. The damaged axons extended new growth into the injury site but didn't completely bridge the gap.

The researchers then added a slight twist to their experiment. It takes the central body of a nerve cell some time to react to an injury along a lengthy axon. The damage signal has to travel down the axon, the cell has to switch genes on and manufacture proteins, and those proteins must then make the journey along the axon.

Recognizing the delay, the investigators decided to sever the peripheral axons of the nerve cells 1 week before the experiment damaged the axons in the spinal cord. "When we pre-injured the peripheral nerves, priming the cells into an actively growing state, and then cut the central axons, we got regrowth right across [the cut] and into the spinal cord above the lesion," says Woolf.

While such regeneration is impressive for spinal cord axons, the researchers have not yet shown that the axons reconnect appropriately and provide any functional recovery for the paralyzed rodents. Other researchers have partially healed spinal cord injuries in animals by blocking the inhibitory myelin proteins or engrafting peripheral nerve cells into the damaged areas (SN: 7/27/96, p. 52).

The approach employed by Neumann and Woolf may not support full recovery from a spinal cord injury, says Ira B. Black of the University of Medicine and Dentistry of New Jersey in Piscataway. Many of the spinal axons travel down from the brain and don't have a peripheral component. It's unclear how scientists could trick these descending fibers into assuming a growing state.

Woolf cautions that the strategy that his group applied to the rodents is not one that physicians would consider. "I don't think anyone would ever take someone with a spinal cord injury and start damaging their peripheral nerves," he says.

Instead, his group plans to isolate the molecular signals generated by injured peripheral axons and determine which ones trigger nerve cells to regenerate.