Chronic ibuprofen administration worsens cognitive outcome following traumatic brain injury in rats.
Traumatic brain injury (TBI) can induce progressive neurodegeneration in association with chronic inflammation. Since chronic treatment with the non-steroidal anti-inflammatory drug (NSAID), ibuprofen, improves functional and histopathologic outcome in a mouse model of Alzheimer's disease (AD), we investigated whether it would also improve long-term outcome following TBI. Anesthetized adult rats were subjected to fluid percussion brain injury. Over the following 4 months the injured animals received ibuprofen per os (formulated in feed) at the approximate doses of 20 mg/kg body wt/day (n=13), 40 mg/kg body wt/day (n=13), or control (feed only, n=12). Sham animals underwent surgery without injury or ibuprofen treatment (n=9). At 4 months post-injury, a Morris water maze task revealed a profound learning dysfunction in all three injured groups compared to the sham group. Surprisingly, the learning ability of injured animals treated with either chronic ibuprofen regimen was significantly worsened compared to non-treated injured animals. However, there was no difference in the extent of progressive atrophy of the cortex or hippocampus between treated and non-treated injured animals. These data may have important implications for TBI patients who are often prescribed NSAIDs for chronic pain.
Browne
Kevin D
KD
Department of Neurosurgery, Center for Brain Injury and Repair, University of Pennsylvania, Philadelphia, PA 19104, USA. kbrowne@mail.med.upenn.edu
Iwata
Akira
A
Putt
M E
ME
Smith
Douglas H
DH
D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001930:Brain Injuries / Q000503:physiopathology*; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007052:Ibuprofen / Q000008:administration & dosage* / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007052:Ibuprofen