scientists at the Karolinska Institute in Stockholm have induced rats' spinal
cords to grow across a gap. It was the first evidence of "true functional
regeneration" in the spinal cord of an adult mammal, according to Wise Young, a
spinal cord specialist from New York University.
Over the years, several researchers thought they had restored severed spinal cords, only to realize later that they had failed to cut the cord entirely in the first place. To skirt this pitfall, the Swedish researchers removed 5 millimeters (.2 inches) of cord -- creating paraplegic rats.
Young, who reviewed the Swedish work for Science magazine (see "Spinal Cord Repair in Adult Paraplegic Rats" in the bibliography), says Henrich Cheng and his colleagues at Karolinska Institute went "through every hoop. This was absolutely the most complete, bulletproof demonstration that we could get."
The demonstration was a milestone, Young told The Why Files. "Nobody is saying the technique is suitable for people yet, but it did overturn one of the most established dogmas of neuroscience -- that central nervous system tissue cannot regenerate." While peripheral nerves, found elsewhere in the body, have a limited ability to grow back after injury, central nervous system tissue does not grow back -- with obvious implications for people with damage to the spinal cord.
Starting in 1982, when Albert Aguayo grew neurons from the central nervous system by placing them in peripheral nerve tissue, researchers began identifying which chemicals prevent -- and accelerate -- the growth of spinal cord. In other words, they have begun to uncover the chemical language controlling nerve growth.
In this highly simplified model, nerve impulses are transmitted from the cell body to a dendrite, across the synapse, along the axon, and into the next cell body.
Cheng and his colleagues used that language in their rat experiments. They began by removing a 5 millimeter section of spinal cord, paralyzing the animals' hind legs. Then they bridged the gap with grafts of peripheral nerve removed from the same animal. Recognizing that the spinal-cord axons would not grow in the presence of other axons, they routed the "patches" to a cell body on the other side of the gap and pasted it into place with fibrin, an organic "glue". They soaked the fibrin with fibroblast growth factor, a chemical that stimulates growth of nerve tissue.
Over the course of several months, axons in the rats' spinal cords grew back across the bridges. By itself, that was startling enough -- as a surgical tour-de-force and definitive proof that central nervous system tissue could actually grow -- in the right conditions.
But there was much more...
Using dye injections, the researchers proved that neurons had grown in both
directions from the cut.
More remarkable, the rats regained the ability to stand.
And most amazing of all, Young says, the axons seemed to find their targets (the muscle they are supposed to control). This achievement was thought to be years or decades in the future -- since it's not clear how nerves find their targets as the fetus develops.
As Young explains, there are three distinct steps to spinal cord regeneration:
Although it's not clear how the axon knows where it's going, Young adds, already we know that one chemical prompts a group of axons to enter what he calls "highway mode" for long-distance travel, and a second chemical signals the axon to head for an "off ramp" and start looking for a target. Together, these chemicals are part of a language that neurons use to control their growth, and which scientists want to press into service in their quest to manipulate nerve growth.