Long-term ibuprofen regimen after brain injury worsens cognition in animal study

Possible implications for traumatic brain injury patients

(Philadelphia, PA) -- Researchers at the University of Pennsylvania School of Medicine found that chronic ibuprofen therapy given after brain injury worsens cognitive abilities. These findings in a preliminary, animal-model study have important implications for traumatic brain injury (TBI) patients who are often prescribed such nonsteroidal anti-inflammatory drugs (NSAIDS) as ibuprofen for chronic pain. The findings appear online this month in Experimental Neurology.

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.

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Study co-authors are Kevin D. Browne, Akira Iwata, and M.E. Putt, all from Penn. The research was supported by grants from the National Institutes of Health.

This release can also be seen at: www.uphs.upenn.edu/news.

PENN Medicine is a $2.9 billion enterprise dedicated to the related missions of medical education, biomedical research, and high-quality patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.

Penn's School of Medicine is ranked #2 in the nation for receipt of NIH research funds; and ranked #3 in the nation in U.S. News & World Report's most recent ranking of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

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