leukotriene-b4 and Infarction--Middle-Cerebral-Artery

Leukotriene B

Topics: Aged; Animals; Arachidonate 5-Lipoxygenase; Cerebral Cortex; Disease Models, Animal; Female; Humans; Infarction, Middle Cerebral Artery; Leukotriene A4; Leukotriene B4; Male; Middle Aged; Rats, Wistar; Severity of Illness Index; Stroke

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

Topics: Animals; Arachidonate 5-Lipoxygenase; Brain; Brain Infarction; Infarction, Middle Cerebral Artery; Leukotriene B4; Lipoxins; Mice; Neuroprotective Agents; PPAR gamma; Rats; Rosiglitazone; Stroke; Thiazolidinediones

To investigate the effects of caffeic acid on early and delayed injuries after focal cerebral ischemia in rats, and the possible relation to 5-lipoxygenase inhibition.. Transient focal cerebral ischemia was induced by middle cerebral artery occlusion in Sprague-Dawley rats. Caffeic acid (10 and 50 mg/kg) was ip injected for 5 d after ischemia. The brain injuries were observed, and the levels of cysteinyl leukotrienes and leukotriene B4 in the brain tissue were measured.. Caffeic acid (50 mg/kg) ameliorated neurological dysfunction and neuron loss, and decreased infarct volume 24 h after ischemia; it attenuated brain atrophy, infarct volume, and particularly astrocyte proliferation 14 d after ischemia. In addition, it reduced the production of leukotrienes (5-lipoxygenase metabolites) in the ischemic hemispheres 3 h and 7 d after ischemia.. Caffeic acid has protective effect on both early and delayed injuries after focal cerebral ischemia in rats; and this effect may partly relate to 5-lipoxygenase inhibition.

Topics: Animals; Antioxidants; Arachidonate 5-Lipoxygenase; Brain; Caffeic Acids; Cysteine; Infarction, Middle Cerebral Artery; Ischemic Attack, Transient; Leukotriene B4; Leukotrienes; Male; Neurons; Neuroprotective Agents; Rats; Rats, Sprague-Dawley