Neurochemical Research

, Volume 36, Issue 1, pp 139–145

RETRACTED ARTICLE: Anti-Inflammatory Effects of Chronic Aspirin on Brain Arachidonic Acid Metabolites

  • Mireille Basselin
  • Epolia Ramadan
  • Mei Chen
  • Stanley I. Rapoport
ORIGINAL PAPER

DOI: 10.1007/s11064-010-0282-4

Cite this article as:
Basselin, M., Ramadan, E., Chen, M. et al. Neurochem Res (2011) 36: 139. doi:10.1007/s11064-010-0282-4
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Abstract

Pro-inflammatory and anti-inflammatory mediators derived from arachidonic acid (AA) modulate peripheral inflammation and its resolution. Aspirin (ASA) is a unique non-steroidal anti-inflammatory drug, which switches AA metabolism from prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) to lipoxin A4 (LXA4) and 15-epi-LXA4. However, it is unknown whether chronic therapeutic doses of ASA are anti-inflammatory in the brain. We hypothesized that ASA would dampen increases in brain concentrations of AA metabolites in a rat model of neuroinflammation, produced by a 6-day intracerebroventricular infusion of bacterial lipopolysaccharide (LPS). In rats infused with LPS (0.5 ng/h) and given ASA-free water to drink, concentrations in high-energy microwaved brain of PGE2, TXB2 and leukotriene B4 (LTB4) were elevated. In rats infused with artificial cerebrospinal fluid, 6 weeks of treatment with a low (10 mg/kg/day) or high (100 mg/kg/day) ASA dose in drinking water decreased brain PGE2, but increased LTB4, LXA4 and 15-epi-LXA4 concentrations. Both doses attenuated the LPS effects on PGE2, and TXB2. The increments in LXA4 and 15-epi-LXA4 caused by high-dose ASA were significantly greater in LPS-infused rats. The ability of ASA to increase anti-inflammatory LXA4 and 15-epi-LXA4 and reduce pro-inflammatory PGE2 and TXB2 suggests considering aspirin further for treating clinical neuroinflammation.

Keywords

Aspirin Neuroinflammation Eicosanoids Arachidonic acid Lipoxin A4 15-epi-lipoxin A4 

Abbreviations

AA

Arachidonic acid

aCSF

Artificial cerebrospinal fluid

COX

Cyclooxygenase

ELISA

Enzyme-linked immunosorbent assay

HETE

Hydroxyeicosatetraenoic acid

icv

Intracerebroventricular

IL

Interleukin

LPS

Lipopolysaccharide

LT

Leukotriene

LXA4

Lipoxin A4

15-epi-LXA4

15-epimeric-lipoxin A4

LOX

Lipoxygenase

PLA2

Phospholipase A2

cPLA2

Cytosolic PLA2

sPLA2

Secretory PLA2

PGE2

Prostaglandin E2

TXB2

Thromboxane B2

NSAID

Non-steroidal anti-inflammatory drug

Copyright information

© Springer Science+Business Media, LLC (outside the USA)  2010

Authors and Affiliations

  • Mireille Basselin
    • 1
  • Epolia Ramadan
    • 1
  • Mei Chen
    • 1
  • Stanley I. Rapoport
    • 1
  1. 1.Brain Physiology and Metabolism Section, National Institute on AgingNational Institutes of HealthBethesdaUSA

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