Monday, Aug. 08, 1983

Brain Healing

Implanting fetal cells in rats

Brain damage is forever, or so doctors once thought, but that longstanding medical axiom is now being proved wrong. In laboratories across the U.S. and Europe, researchers are finding that by creating the right chemical environment, and in some cases implanting new cells in the brain, damaged nervous systems can be coaxed to regenerate. Even more encouraging is the discovery, so far shown only in animals, that cellular regrowth can restore lost mental functions, and, in addition, improve memory and learning.

The latest achievement in this promising field is the work of Dr. Donald Stein and three colleagues at Clark University in Worcester, Mass. As reported in last week's issue of Science, the group attempted to restore mental functioning in 21 rats whose brains had been damaged by removal of large sections of the frontal cortex. This section of the brain is involved in the learning of complex spatial relationships. Typically, rats sustaining such a severe injury would take 18 days or more to master a maze that required them to alternate right and left turns in the correct order to get a drink of water. "The rat has got to remember what he did the last time and then do the opposite," Stein explains. Normal rats can learn the task in just 2 1/2 days.

Before attempting to repair the brain damage, Stein's team waited a week to allow for the natural accumulation of healing proteins called nerve growth factors. Then they implanted a pinhead-size lump of tissue that had been taken from the frontal cortex of normal rat embryos. The researchers used fetal cells because they are rich in growth factors and adapt easily to a new environment. Result of the operation: the brain-damaged rats were able to learn the maze in just 8 1/2 days. While this is still slower than normal, says Stein, "the transplant was clearly producing some degree of functional recovery." Stein later found that new connections had grown between the transplanted tissue and the rest of the brain.

According to Stein, the immediate lesson of his group's experiment is "that there is much more capacity for response to brain injury than previously thought." The same conclusion has been reached by researchers who have regenerated nerve fibers in other parts of animals' brains as well as in their spinal cords. At Saint Elizabeths Hospital in Washington, D.C., for instance, Neuroscientist William Freed has treated rats with fetal cell implants to relieve symptoms resembling Parkinson's disease in humans. The implanted cells are capable of producing dopamine, a vital brain chemical lacking in the afflicted rats and in Parkinson's patients. Such techniques used with humans, some researchers believe, may lead to a cure for Parkinson's disease within five to ten years. Eventually, it may also become possible to repair the spinal cords of paraplegics and regenerate parts of the extensively damaged brains of patients with Alzheimer's disease, Huntington's chorea, multiple sclerosis and other degenerative disorders.

Before such steps can be attempted, however, certain ethical questions surrounding the use of tissue from human fetuses must be resolved. The sensitivity of this issue may be dramatized this week, when a funding bill for the National Institutes of Health, which finances many such experiments, is scheduled to come before the House of Representatives. California Republican William Dannemeyer plans to offer an amendment that would drastically increase the already stringent restrictions on the use of human fetuses for research purposes. A similar measure was passed by the House last year but defeated in the Senate. Congressman Henry Waxman, who opposes the amendment, argues that "fetal research saves lives, prevents or cures chronic diseases and makes pregnancy safer. As a result of such work, reductions in infant mortality and treatments for diabetes, as well as for brain disorders, are on the horizon."

Researchers, hoping to avoid controversy, are looking for alternatives to fetal tissues. In the case of Parkinson's disease, says Freed, it may be possible to transplant dopamine-secreting cells taken from the patient's own adrenal gland. Other approaches were discussed at a conference on fetal cell research last month in Brookline, Mass. Among them: the possibility of altering monkey fetal cells for use in humans. Ultimately, as researchers become able to identify the chemicals that give fetal cells their regenerative powers, they may find ways to synthesize these substances or to develop cell cultures that produce them in the lab. Unlocking these secrets "is the best hope we have for those who have lost brain cells because of a stroke, an injury or a degenerative disease," says Vernon Mark, director of neurosurgery at Boston City Hospital. "Right now," he adds, "it's the only game in town." This file is automatically generated by a robot program, so viewer discretion is required.