Synthesis of Lipoxin A4by 5-Lipoxygenase Mediates PPARγ-Dependent, Neuroprotective Effects of Rosiglitazone in Experimental Stroke

• DOI: 10.1523/jneurosci.5529-08.2009
• Publication Date: 2009-03-25T17:58:01Z
• Authors: Mónica Sobrado; Marta P. Pereira; Iván Ballesteros; Olivia Hurtado; David Fernández-L...; Jesús M. Pradillo; Javier R. Caso; José Vivancos; Florentino Nombela; Joaquín Serena; Ignacio Lizasoain; María A. Moro
• Keywords: Rosiglitazone; Lipoxin

Peroxisome proliferator-activated receptors gamma (PPARγ) are nuclear with essential roles as transcriptional regulators of glucose and lipid homeostasis. PPARγ also potent anti-inflammatory receptors, a property that contributes to the neuroprotective effects agonists in experimental stroke. The mechanism these beneficial actions, however, is not fully elucidated. Therefore, we have explored further actions agonist rosiglitazone stroke induced by permanent middle cerebral artery occlusion (MCAO) rodents. Rosiglitazone brain 5-lipoxygenase (5-LO) expression ischemic rat brain, concomitantly neuroprotection. increased lipoxin A 4 (LXA ) levels inhibited MCAO-induced production leukotriene B4 (LTB ). Furthermore, pharmacological inhibition and/or genetic deletion 5-LO rosiglitazone-induced neuroprotection downregulation inflammatory gene expression, LXA synthesis activity Finally, caused neuroprotection, which was partly antagonist T0070907, isolated nuclei, showing for first time has agonistic actions. Altogether, our data illustrate some attributable de novo 5-LO, able induce switch from proinflammatory LTB proresolving . Our study suggests novel lines such interest lipoxin-like drugs or use molecules prognostic diagnostic markers pathologies inflammation involved,