(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
“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.
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.
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