New York Times; Late Edition (East Coast), New York
Jul 26, 1996
Start Page: A.14
ISSN: 03624331
Text: Copyright New York Times Company Jul 26, 1996 Author: Gina Kolata
In what one scientist called a tour de force, a group of researchers in Sweden has succeeded for the first time in growing nerve cells across gaps in severed spinal cords in rats.
The work is startling and demands to be repeated by others, said experts in the field, who noted that some previous reports of similar achievements had failed to pan out. It is merely the first step toward the distant goal of curing patients with injured spinal cords, they said, but the work shows that such a goal may not be an impossible dream.
The study, by Dr. Lars Olson, a professor of neurobiology; Dr. Henrich Cheng, a neurosurgeon; and Dr. Yihai Cao, a molecular biologist, at the Karolinska Institute in Sweden, is being published today in the journal Science. It involved adult rats whose spinal cords were severed, leaving a gap of about one-fifth of an inch.
Using microsurgery, Dr. Cheng sewed a bridge of slender nerve cells across the gap, to guide the severed nerves in their effort to regenerate. He obtained the nerves for the bridge from the animals' chests.
The investigators glued the bridge down at either end with fibrin, the sticky substance in blood that shows up on a wound just before a scab forms. They had first mixed the fibrin with fibroblast growth factor, a substance that encourages cells to grow.
Then they watched for three months while the injured animals dragged their hind legs behind them, like dead weights. Finally, Dr. Olson said, he noticed a change in the animals that had gotten the complete repair treatment, but not in control animals that had no surgery or only parts of it. The treated animals, he said, started to flex their legs.
Dr. Olson, who had been working on spinal cord repair for almost three decades, said, "That was one of the best moments in my scientific life."
As time went by, he said, the rats continued to improve.
"They started to move their hind limbs, as if they were attempting to use them for walking," Dr. Olson said.
A year after the surgery, the treated animals could partly support their weight and could move their legs, although they were not walking normally. When the researchers did anatomical studies, injecting dyes into the nerve tracts after the rats had been killed, they found that nerves had regrown from either end of the injury, growing down to the tail and up to the brain.
Dr. Jerry Silver, a professor of neuroscience at Case Western Reserve University in Cleveland, said he was taken aback by the results.
In cutting away a large section of the rats' spinal cords, Dr. Silver said, "they've done about the worst thing to a spinal cord that you can do."
"The model is rather dramatic," he said. "They've duplicated the worst thing possible and then some."
And then, Dr. Silver said, the investigators did what many thought was impossible - they got the nerves to regenerate across the gap and to function again.
"I think it's pretty incredible," Dr. Silver said.
Dr. Wise Young, a professor of neurosurgery, physiology and neuroscience at New York University, who wrote an accompanying editorial in Science, was also impressed.
"I think this paper shows not only that regeneration is possible but it also shows that the task will be easier than we ever anticipated," Dr. Young said. "Probably very few axons crossed the gap, probably no more than 10 percent."
And that means, he said, that "we don't have to regrow the whole spinal cord." It means that repairing spinal cord injury "is in the realm of possibility."
The field of spinal cord regeneration has been plagued by reports of miraculous cures of animals whose cords were severed and who subsequently walked and even scampered about. None of those reports panned out.
"The first thing about spinal cord research is to be very, very skeptical about it," said Dr. John W. Commissiong, a neurobiologist at the National Institute of Neurological Diseases and Stroke.
In many previous reports of cures, Dr. Commissiong said, investigators did not even sever the animals' spinal cords, although they thought they had done so.
"In general, you don't see what you are doing because there is an enormous amount of bleeding," he said. And when researchers accidentally left just 5 percent of nerve fibers intact, he said, "after six months, the rats walked normally."
As researchers became more sophisticated in their methods, the claims of healed spinal cords all but ceased, said Dr. Paul Reier, a professor of neurosurgery and neuroscience at the University of Florida College of Medicine in Gainesville, and the task of regenerating severed spinal cord nerves began to look nearly hopeless.
Dr. Young said that the work was so discouraging that "there may be just 20 labs in the U.S. working on spinal cord injury, compared to AIDS where there are literally thousands of labs working on the problem."
A crucial factor in his success, Dr. Olson said, was that his group purposely guided nerve cells to Grow from white matter, the outer, insulated layer of the spinal cord, to gray matter, the interior part of the cord.
Normally, nerve cells grow on the outside of the spinal cord.
"That's their highway," Dr. Silver said. When nerves branch off to connect with a muscle, for example, they veer into the gray matter and then out of the spinal cord.
But white matter contains inhibitors that stymie nerve growth, researchers have found. By constructing the nerve bridges so they went from white matter to gray matter, the researchers apparently bypassed the nerve growth inhibitors. The regenerating nerves grew across the gap in the spinal cord, entered the gray matter on the other side, and migrated down the cord at the interface between the white matter and the gray matter.
"That tells us that the white matter inhibitors that are thought to be all over the spinal cord are not so inhibitory after all," Dr. Silver said.
Dr. Silver said that what surprised him most about that work is that it was so simple.
"We're in an age of molecular biology, and they used just a simple surgical procedure to make a bridge and then bolted it down with glue," he said.
But Dr. Reier said that the very simplicity of the work made him a little leery.
"If this is true, we've been missing the point for years," he said. "It's not like the result here is built on a huge degree of biotech. What it is is a surgical tour de force."
And so, Dr. Reier said, it is crucial that the work be replicated by other laboratories.
"If this is absolutely true, it's remarkable," he' said. "This work is coming from a good laboratory, but they're talking about a degree of regeneration that is pretty remarkable. And getting fibers to grow across a lesion is pretty astounding. Then, to say the animal got some degree of function is even more astounding." Captioned as: "Microsurgery: Bridging a Spinal Gap" gives a cross section of a spinal cord and identified many of its parts. (Dr. Wise Young/New York University Medical School; Dr. Jerry Silver/Case-Western Reserve; Dr. Lars Olson/Science)
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