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Discovery of pathway in learning impairment caused by liver disease may lead to drug treatment

Liver disease sometimes causes hepatic encephalopathy, which involves brain damage, personality changes, and intellectual impairment due to hyperammonemia (high levels of ammonia in the blood). However, the mechanisms involved in both learning and how liver disease leads to learning impairment are unclear.

In a new study led by Vicente Felipo of the Laboratory of Neurobiology at the Fundacion Valenciana de Investigaciones Biomedicas in Valencia, Spain and published in the February 2005 issue of Hepatology, researchers hypothesized that impaired learning was due to a defect in the glutamate-nitric oxide-cGMP pathway in the brain and that administering sildenafil to increase cGMP would restore learning ability. Sildenafil, commonly known as Viagra, is known to prevent the destruction of cGMP and allow it to accumulate in the body. Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD), published by John Wiley & Sons, Inc. is available online via Wiley InterScience at http://www.interscience.wiley.com/journal/hepatology.

Researchers examined four groups of rats in their study: rats in which they constructed portacaval shunts (a treatment used to treat high blood pressure in the liver due to liver disease that is believed to be one of the causes of hepatic encephalopathy, and also a model of chronic liver failure in rats); rats with portacaval shunts that were given sildenafil; rats that were fed an ammonium-containing diet; and rats that were fed the diet and given sildenafil. They also used control groups consisting of rats fed a normal diet both with and without sildenafil. All animals were subjected to a maze learning test four weeks following surgery or from the date when drug treatment began. Levels of both cGMP and ammonia in brain were measured using a microdialysis probe.

Results showed that while rats with the portacaval
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Contact: David Greenberg
dgreenbe@wiley.com
201-748-6484
John Wiley & Sons, Inc.
19-Jan-2005


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