Low-dose aspirin (acetylsalicylate) prevents increases in brain PGE(2), 15-epi-lipoxin A4 and 8-isoprostane concentrations in 9 month-old HIV-1 transgenic rats, a model for HIV-1 associated neurocognitive disorders

BACKGROUND: Older human immunodeficiency virus (HIV)-1 transgenic rats are a model for HIV-1 associated neurocognitive disorders (HAND). They show behavioral changes, neuroinflammation, neuronal loss, and increased brain arachidonic acid (AA) enzymes. Aspirin (acetylsalicylate, ASA) inhibits AA oxidation by cyclooxygenase (COX)-1 and COX-2. HYPOTHESIS: Chronic low-dose ASA will downregulate brain AA metabolism in HIV-1 transgenic rats. METHODS: Nine month-old HIV-1 transgenic and wildtype rats were given 42 days of 10 mg/kg/day ASA or nothing in drinking water; eicosanoids were measured using ELISAs on microwaved brain extracts. RESULTS: Brain 15-epi-lipoxin A4 and 8-isoprostane concentrations were significantly higher in HIV-1 transgenic than wildtype rats; these differences were prevented by ASA. ASA reduced prostaglandin E(2) and leukotriene B(4) concentrations in HIV-1 Tg but not wildtype rats. Thromboxane B(2), 15-HETE, lipoxin A(4) and resolvin D(1) concentrations were unaffected by genotype or treatment. CONCLUSION: Chronic low-dose ASA reduces AA-metabolite markers of neuroinflammation and oxidative stress in a rat model for HAND.