Novel Docosanoids Inhibit Brain Ischemia-Reperfusion-mediated Leukocyte Infiltration and Pro-inflammatory Gene Expression*

By V. Marcheselli, Song‐Pyo Hong, Walter J. Lukiw, Xiaolin Tian, K. Gronert, Alberto E. Musto, Mattie Hardy, J. M. Giménez, Chia Nan, C. Serhan and 1 more. Journal of Biological Chemistry, 2003

806 citations recorded by the source corpus.

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, NFκB, 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-β-induced NFκB 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.

Subfields: Biochemistry, Nutrition and Dietetics, Surgery

View Paper: https://www.semanticscholar.org/paper/6c27de3e116b7f8bd086f0feb4e059d6ada81fd6

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Biochemistry

1. P. Calder
2. C. Serhan
3. D. Gilroy
4. Undurti N. Das
5. Chia Nan
6. C. Buckley
7. S. Leng
8. H. Aukema

In Nutrition and Dietetics

1. P. Calder
2. C. Serhan
3. D. Gilroy
4. Undurti N. Das
5. Chia Nan
6. C. Buckley
7. D. Tocher
8. S. Leng

In Surgery

1. P. Calder
2. C. Serhan
3. D. Gilroy
4. C. Buckley
5. D. Tocher
6. D. Mozaffarian
7. B. Levy
8. Christopher K. Glass

Citations in the corpus

• Pro-Resolving lipid mediators and Mechanisms in the resolution of acute inflammation (2014, background): “MaR1’s potent antiinflammatory and pro-resolving actions were recently confirmed in murine colitis, where it is protective in both DSS and TNBS models of colitis (Marcon et al., 2013).”
• A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. (2005, methodology): “The unesterified DHA pool size assessed by liquid chromatography–photodiode array–electrospray ionization–tandem mass spectrometry–based (LC-PDA-ESI-MS-MS–based) lipidomic analysis (5, 6) (Figure 1I) showed that neither Aβ42 nor sAPPα was able to promote unesterFigure 2 Aβ42-induced apoptosis is inh”
• Essential fatty acids: biochemistry, physiology and pathology (2006, background): “Resolvins inhibit brain ischemia-reperfusion injury [92].”
• Advances in Our Understanding of Oxylipins Derived from Dietary PUFAs. (2015, positive): “LOX oxylipins 14,20-DiHDoHE Inhibits PMN infiltration in the mouse peritonitis model (101) 14,21-DiHDoHE Enhances wound healing in murine models (313, 314) 4-HDoHE Inhibits endothelial cell proliferation and sprouting angiogenesis in mouse model of oxygen-induced retinopathy (315) 7-HDoHE Activates ”
• Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators (2008, background): “and are particularly interesting because the brain, synapses and retina are highly enriched in DH”
• Fish oil replacement and alternative lipid sources in aquaculture feeds (2010, positive): “DHA-derived D-resolvins also have antiinflammatory effects (Marcheselli et al., 2003).”
• Polyunsaturated fatty acids and inflammatory processes: New twists in an old tale. (2009, background): “2) and these too are anti-inflammatory [25] [26] [27].”
• Resolution of inflammation: the beginning programs the end (2005, positive): “, as well as newly identified families of lipid mediators generated from omega-3 polyunsaturated fatty acid called resolvins (resolution-phase interaction products) and protectin”
• The Various Roles of Fatty Acids (2018, background): “The ratios between the different FA present in the organisms are therefore more reliable for their identification than the use of individual markers [179,199,224].”