Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression

J Biol Chem. 2003 Oct 31;278(44):43807-17. doi: 10.1074/jbc.M305841200. Epub 2003 Aug 15.


Ischemic stroke triggers lipid peroxidation and neuronal injury. Docosahexaenoic acid released from membrane phospholipids during brain ischemia is a major source of lipid peroxides. Leukocyte infiltration and pro-inflammatory gene expression also contribute to stroke damage. In this study using lipidomic analysis, we have identified stereospecific messengers from docosahexaenoate-oxygenation pathways in a mouse stroke model. Aspirin, widely used to prevent cerebrovascular disease, activates an additional pathway, which includes the 17R-resolvins. The newly discovered brain messenger 10,17S-docosatriene potently inhibited leukocyte infiltration, NFkappaB, and cyclooxygenase-2 induction in experimental stroke and elicited neuroprotection. In addition, in neural cells in culture, this lipid messenger also inhibited both interleukin 1-beta-induced NFkappaB activation and cyclooxygenase-2 expression. Thus, the specific novel bioactive docosanoids generated in vivo counteract leukocyte-mediated injury as well as pro-inflammatory gene induction. These results challenge the view that docosahexaenoate only participates in brain damage and demonstrate that this fatty acid is also the endogenous precursor to a neuroprotective signaling response to ischemia-reperfusion.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Aspirin / pharmacology
  • Brain / pathology*
  • Cells, Cultured
  • Cerebral Arteries / pathology
  • Cyclooxygenase 2
  • Docosahexaenoic Acids / chemistry*
  • Docosahexaenoic Acids / pharmacology*
  • Hippocampus / metabolism
  • Humans
  • Immunohistochemistry
  • Interleukin-1 / metabolism
  • Isoenzymes / metabolism
  • Leukocytes / metabolism*
  • Leukocytes / pathology
  • Lipid Peroxidation
  • Membrane Proteins
  • Mice
  • Microscopy, Fluorescence
  • Models, Chemical
  • NF-kappa B / metabolism
  • Neurons / metabolism
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Reperfusion Injury*
  • Signal Transduction
  • Stem Cells / metabolism
  • Time Factors


  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-1
  • Isoenzymes
  • Membrane Proteins
  • NF-kappa B
  • Docosahexaenoic Acids
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Aspirin