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Because several studies in animals and humans have shown that long-term use of ibuprofen for inflammation improves outcome for Alzheimer's patients by reducing symptoms and delaying the onset of dementia, the researchers investigated whether ibuprofen improved long-term cognitive outcome in brain-injured animals.

Over four months, rats received ibuprofen in their food proportional to doses given to humans. In the two groups of injured rats (one fed ibuprofen and the other not), there was a significant overall deficit in the animals' ability to find an underwater platform in a Morris water maze, a common test used to assess cognitive ability in animals.

"But to our surprise, we found that the injured rats given ibuprofen were far worse compared to the injured rats that had no treatment at all," says lead author Douglas H. Smith, MD, Director of the Center for Brain Injury and Repair. "Although most untreated injured animals could find the platform, they were much slower to learn its location than non-injured animals. In contrast, almost none of the treated, injured animals could find the platform at all."

However, there were no outward signs of difference in the extent of atrophy in the hippocampus or cortex of treated versus non-treated injured rats. Although ibuprofen treatment did reduce chronic inflammatory changes in the brains of injured animals, that did not seem to have an influence over the extent of damage to the brain regions associated with learning and memory.

This initial study demonstrates that the effects of long-term treatment with NSAIDS like ibuprofen after a head injury are poorly understood. "We have to remember these are animal studies, and what we can take home is that we need further examination of potential negative effects in patients," says Smith. "I hope these findings inspire studies in patients to evaluate the safety, efficacy, and potential long-term problems with cognition of chronic ibuprofen use in TBI patients."

In Alzheimer's patients, chronic ibuprofen appears to be beneficial by delaying onset and severity of symptoms. Similarly, chronic ibuprofen therapy in a mouse model of Alzheimer's disease reduces plaque build-up in the brain and improves function. However, finding that this same approach to treatment worsens the outcome in an animal model of TBI may have important implications for TBI patients who are often prescribed NSAIDS for chronic pain. With few alternative over-the-counter pain medicines available to these patients, further investigation is essential, says Smith.

Contact: Karen Kreeger karen.kreeger@uphs.upenn.edu 215-349-5658 University of Pennsylvania School of Medicine

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