Apr. 22, 2003 MINNEAPOLIS / ST. PAUL (April 18, 2003) -- University of Minnesota researchers have found that a non-toxic bile acid produced in the body prevents apoptosis, or programmed cell death, in rats after a type of stroke, an intracerebral hemorrhage (ICH). The finding, published in the journal Proceedings of the National Academy of Sciences USA (PNAS) on April 21, may eventually lead to treatment in patients with hemorrhagic stroke and other acute brain injuries. ICH is a devastating acute neurological disorder, currently without effective treatment, in which a significant loss of neuronal cells is thought to occur by apoptosis.
In the study, led by Clifford Steer, M.D., director of the University's molecular gastroenterology program, a dose of tauroursodeoxycholic acid (TUDCA) was administered into the carotid artery before or up to six hours after ICH in rats. Researchers found that TUDCA significantly reduced the injury associated with ICH.
"We found that apoptosis decreased by approximately 50 percent," said Steer, "and this translated into about a 50 percent decrease in lesion volume."
TUDCA is able to cross the blood / brain barrier, something many molecules are unable to do, resulting in decreased apoptosis in the section of the brain affected by ICH and improving the cell and neurological function in the rats. "We're extremely encouraged by the neuroprotective function of TUDCA and will be examining its potential in future studies," said Walter Low, Ph.D., professor of neurosurgery and co-investigator in the study.
"Not only does TUDCA cross the blood / brain barrier," said Steer, "but it also induces survival pathways in cells when they are injured and simultaneously inhibits the destructive pathways. This bile acid is particularly unique in its ability to maintain the integrity of mitochondria that is so important for normal cell function."
"What's exciting about TUDCA, in addition to its remarkable anti-apoptotic quality, is that it's made in our own bodies and causes no significant side effects when given as a drug to animals," says Steer. The bile acid's anti-apoptotic qualities were originally discovered in Steer's laboratory and have been found to be effective in inhibiting cell death in transgenic mice with Huntington's disease.
Orally administered ursodeoxycholic acid, the parent molecule, is already FDA-approved for the treatment of primary biliary cirrhosis.
Other authors of the study include Cecilia M.P. Rodrigues, Susana Sola, Zhenhong Nan, Rui E. Castro, and Paulo S. Ribeiro.
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