Chronic liver failure impairs cognitive function, but a new study has found that treatment with Ibuprofen, an anti-inflammatory restores learning ability in affected rats.
The study was conducted by a team of researchers led by Vicente Felipo at the Centro de Investigacion Principe Felipe in Valencia, Spain.
Earliers studies have shown that high ammonia levels and inflammation may cooperate in the brain alterations seen in hepatic encephalopathy, a potentially reversible neuropsychiatic abnormality in the setting of liver failure.
As part of this study researchers examined whether alterations associated with inflammation were involved in learning impairment in rats who had chronic liver failure due to insertion of a porta-caval shunt (PCS).
PCS is a treatment for high blood pressure in the liver in which a shunt is created surgically between the portal vein and the inferior vena cava so that blood from the abdominal organs can bypass the liver.
The study found that PCS rats had a decreased ability to learn a Y maze, but their ability to learn the maze was completely restored after administration of ibuprofen.
PCS rats showed both high ammonia levels and inflammation, but reducing the inflammation improved their learning ability, even though ammonia levels remained high.
The researchers suggested that this was due to ibuprofen's ability to restore the function of a pathway in the brain known as the glutamate-NO-cGMP pathway.
Researchers also found that ibuprofen normalized the activity of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX), two enzymes that play a role in inflammation in the cerebral cortex.
"The data presented here, using ibuprofen as an experimental tool to decrease inflammation, clearly show that decreasing inflammation completely restores the ability to learn the Y maze task in a rat model of hepatic encephalopathy. This supports the idea that reducing inflammation would improve cognitive function in patients with hepatic encephalopathy. It would be convenient to look for procedures to decrease inflammation without having the possible secondary effects of NSAIDS, maybe new specific inhibitors of COX with no or less secondary effects could have beneficial effects," the authors said.
The findings of the study were published in the August issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD).