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.
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.
Source:
University of Pennsylvania School of
Medicine
Published on 25th
JULY 2006
