The brain consequences of systemic inflammation were not fully alleviated by ibuprofen treatment in mice.

Abstract

Extensive data point to the immune system as an important factor underlying the pathogenesis of brain diseases. Epidemiological studies have shown that long-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) significantly reduces the onset and progression of Alzheimer's disease. The present study aimed to investigate whether ibuprofen (IBU) is able to prevent the long-lasting alterations of brain function induced by systemic inflammation. Mice received intraperitoneal injections of lipopolysaccharide (LPS; 250µg/kg/day) for seven consecutive days. Ibuprofen administration (40mg/kg/day) was started three days before the LPS injections and continued until the last day of LPS injection. Within the next 2 weeks, mice performances on the behavioral tests were evaluated, and then brain tissue samples for biochemical analyses were collected. The findings showed that ibuprofen significantly improved mice's performance in the passive avoidance test and reduced anxiety- and depressive-like behaviors. However, ibuprofen could not significantly improve spatial memory in the Morris water maze test and recognition ability in the novel object recognition test. TNF-α and IL-1β cytokines levels and malondialdehyde (MDA) concentration in the hippocampal tissues of LPS-treated mice were significantly lowered by ibuprofen treatment, whereas no significant effects on IL-10 production and hippocampal BDNF levels were observed. In addition, ibuprofen did not significantly reduce amyloid-β1-40 levels in the hippocampus of LPS-treated animals. Overall, the findings of the present study suggest that some, but not all, of the adverse effects of systemic inflammation are alleviated by ibuprofen treatment.