title: Low-dose aspirin (acetylsalicylate) prevents increases in brain PGE2, 15-epi-lipoxin A4 and 8-isoprostane concentrations in 9 month-old HIV-1 transgenic rats, a model for HIV-1 associated neurocognitive disorders.
abstract: 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.
  
  
  OBJECTIVE
  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 10mg/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 E2 and leukotriene B4 concentrations in HIV-1 Tg but not wildtype rats. Thromboxane B2, 15-HETE, lipoxin A4 and resolvin D1 concentrations were unaffected by genotype or treatment.
  
  
  CONCLUSIONS
  Chronic low-dose ASA reduces AA-metabolite markers of neuroinflammation and oxidative stress in a rat model for HAND.
authors: Brain Physiology and Metabolism Section, Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Helene C
authors: HC
authors: Blanchard
authors: Brain Physiology and Metabolism Section, Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Ameer Y
authors: AY
authors: Taha
authors: Brain Physiology and Metabolism Section, Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: sir@mail.nih.gov.
authors: Stanley I
authors: SI
authors: Rapoport
authors: Brain Physiology and Metabolism Section, Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Zhi-Xin
authors: ZX
authors: Yuan
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001241:Aspirin / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D004195:Disease Models, Animal; D015497:HIV-1 / Q000235:genetics; D044045:Lipoxins / Q000378:metabolism; D008297:Male; D019965:Neurocognitive Disorders / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D055647:Rats, Transgenic; D014662:Vasoconstrictor Agents / Q000378:metabolism
chemical_list: C512487:15-methyl-lipoxin A4; D000894:Anti-Inflammatory Agents, Non-Steroidal; D044045:Lipoxins; D014662:Vasoconstrictor Agents; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D015232:Dinoprostone; D001241:Aspirin
keywords: 8-Isoprostane; Brain; Chronic aspirin; HIV-1; PGE(2); Rat
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