Originally created 06/26/02

Natural compound may help brain recover from stroke



WASHINGTON -- Injecting rats with a natural chemical called inosine caused the growth of new nerve tissue and the restoration of some functions lost after a stroke, researchers report.

In a study appearing this week in the Proceedings of the National Academy of Sciences, researchers in Boston found that inosine caused the undamaged side of the brain to develop new nerve circuits that helped to restore function in rats who lost the ability to control their legs after induced strokes.

"Inosine stimulates the damaged nerve cells to form new connections that partially take the place of the ones lost in the stroke," said Larry Benowitz, a researcher at Boston's Children's Hospital and an associate professor of neurology at Harvard Medical School.

Inosine is a nucleosine, one of the basic compounds that make up cells; dietary sources include yeast and organ meats, such as liver. In effect, said Benowitz, inosine causes the brain to at least partially "rewire" itself to compensate for the loss of function caused by the stroke.

The most common form of stroke occurs when a blood vessel is blocked, shutting down blood flow to brain tissue. Brain cells die, leading to a loss of the function that those cells once controlled. Stroke patients commonly lose control of limbs, speech or other body functions. A massive stroke can kill.

Stroke happens to about 750,000 Americans annually and is the third leading cause of death, claiming about 160,000 lives annually. Rehabilitation and treatment for survivors cost about $30 billion a year.

Benowitz said that inosine may work by boosting a feeble tendency by the brain to repair the damage of a stroke.

"After a stroke, humans do show some recovery," he said. "There is a hint in the literature that there is some compensatory growth in the intact part of the brain that allows (some recovery). We think that inosine is amplifying that type of growth."

In the study, the researchers induced strokes in a group of laboratory rats, then put the animals through tests that determined how well they could control the movement of their paws.

The researchers then injected about half the rats with inosine and retested the animals. Benowitz said that after 19 days, the treated rats had nearly normal use of their paws, while only about half of the untreated animals recovered some function.

Benowitz said that microscopic examination of the lab animals' brains showed a growth of new nerve tissue and connections in the unaffected side of the brain.

"The stroke damages neurons on one side of the brain and the growth takes place on the other side," said Benowitz. "The neurons on the good side of the brain sprout new branches that go into the areas that have lost their normal function."

He said there is no indication that inosine causes harmful side effects in the test rats, but studies are under way to determine if the compound leads to excessive nerve growth.

Benowitz said that although it hasn't been proved that inosine will have the same effect in humans, earlier studies have shown that the rat brain, on a molecular level, is very similar to the human brain.

Dr. Lawrence M. Brass, a Yale Medical School professor and the science adviser to the National Stroke Association, said the Benowitz study "is interesting, exciting and important" because it suggests strongly that the brain can repair itself following a stroke.

"It appears that the brain has the capability of doing more rewiring that we thought possible," said Brass. "This shows that inosine not only encourages rewiring, but that the rewiring does work."

Brass said, however, that inosine should be tested in higher animals, such as baboons, before it is tested in humans.

"We need to have one higher animal between rats and humans," he said. "If the results are as potent as they appear, this would not be a major delay."

Boston Life Sciences, a biotechnology company, partially financed the study and holds the development rights to inosine. Benowitz said he is a paid consultant of the company and has some stock interest in it.

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Proceedings of the National Academy of Sciences: http://www.pnas.org