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Compounds Found to Protect Rabbits From Cerebral Palsy
Date:2/25/2009

Discovery called exciting, but human application remains elusive, expert says

WEDNESDAY, Feb. 25 (HealthDay News) -- In experiments with rabbits, a team of scientists has created two chemical compounds that appear to protect a fetus from developing cerebral palsy from a lack of oxygen.

"It is known that if you have too much nitric oxide in the brain, which can be produced during hypoxia, it leads to fetal neurodegeneration," said lead researcher Richard B. Silverman, a chemistry professor at Northwestern University.

If such an event occurs during pregnancy, it can lead to brain damage in the fetus that can result in cerebral palsy, Silverman said. "This can happen right at the end of pregnancy," he explained.

Common causes of hypoxia include a pinched umbilical cord or a cord wrapped around the fetus's neck or shoulder.

The report was published online Wednesday in the Annals of Neurology.

Silverman's team developed two compounds that block an enzyme in brain cells that produces nitric oxide. At normal levels, nitric oxide is a neurotransmitter, which is important for brain functioning, but at high levels it can damage brain tissue. An excess of nitric oxide in the brain is believed to play a role in cerebral palsy.

In experiments with rabbits, excess nitric oxide caused most of the fetuses to die, and those that survived were severely brain-damaged, Silverman said.

"If you administer the compounds that we made a half-hour prior to the hypoxic insult, you can protect the fetus from neurodegeneration," Silverman said. All the animals treated with the compounds lived, and those given placebo died. Among animals given just one of the compounds, up to 80 percent were born normal, Silverman said.

Silverman said that he thinks the compounds can be used to treat infants with compromised oxygen levels before cesarean delivery. "The sooner you can protect the fetal brain from nitric oxide, the less neurodegeneration you will have," he said.

The next step is to experiment with these compounds in sheep, Silverman said. "It's a long way to humans," he noted.

Dr. Ernest Graham, an assistant professor of maternal-fetal medicine at Johns Hopkins School of Medicine in Baltimore, agrees that using the compounds in clinical practice is a long way off.

"This is very exciting stuff," Graham said. However, he added, how it could be used remains elusive.

Graham said that perhaps the compounds could be used after delivery for infants who appear lethargic or "floppy," or have poor muscle tone, he said. Giving it before delivery would mean giving it to many babies who don't need it, he noted.

Using it before delivery on an infant with a prolapsed cord or similar problem might not be practical, Silverman said. "With these kids, things are moving so fast, I don't know it is going to be practical to give an additional drug," he said.

Cerebral palsy is caused by an injury to the brain before, during or shortly after birth, although it typically is not diagnosed until after the age of 1. Approximately 750,000 children and adults in the United States have a form of cerebral palsy, with most having been born with the condition.

More information

The U.S. National Institute of Neurological Disorders and Stroke has more on cerebral palsy.



SOURCES: Richard B. Silverman, Ph.D., John Evans Professor of Chemistry, Northwestern University, Evanston, Ill.; Ernest Graham, M.D., assistant professor, maternal-fetal medicine, Johns Hopkins School of Medicine, Baltimore; February 2009, Annals of Neurology


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