Angiotensin receptor blocker, losartan ameliorates neuroinflammation and behavioral consequences of lipopolysaccharide injection

Aims: Neuroinflammation has a critical role in brain diseases. Angiotensin II (Ang II) is an important player in inflammation via stimulating of Ang II type 1 receptor (AT1R). In this study, the effects of losartan, an Ang II receptor blocker, on the brain inflammation, oxidative stress and behavioral consequences of lipopolysaccharide (LPS) injection were investigated. Main methods: Rats were intraperitoneally (i.p.) injected with 1 or 3 mg/kg losartan or saline for 24 continuous days. At the day 4 of the experiment, rats received a single i.p. injection of 1 mg/kg LPS or saline and two weeks later they received the second LPS challenge which they were administrated with 0.5 mg/kg LPS or saline for 7 continuous days. At the 72 h after the last treatment, the behavioral tests were conducted. The brains were removed for the biochemical analyses. Key findings: LPS injection increased IL (interleukin)-6, malondialdehyde (MDA) and nitric oxide (NO) metabolites and reduced thiol content and activities of catalase (CAT) and superoxide dismutase (SOD) in the cortex and hippocampus. Moreover, LPS injection impaired fear memory in the PA (passive avoidance), induced anhedonia in the SPT (sucrose preference test) and increased immobility time in the FST (force swimming test). Pretreatment with 3 mg/kg losartan decreased the brain IL-6, MDA and NO metabolites while, increased the anti-oxidant parameters and improved the performances of rats in the PA, SPT and FST. Significance: The results indicated that systemic inflammation had deleterious long-lasting consequences on brain, which were reversed by pretreatment with losartan.