Lipoxin A4 analogue protects brain and reduces inflammation in a rat model of focal cerebral ischemia reperfusion

Inflammation, which is known to be detrimental to the neurological outcome during the acute phase after ischemia, provides a potential preventative or therapeutic approach for acute stroke. Lipoxins are endogenous lipoxygenase derived eicosanoids and evokes protective actions in a range of pathophysiologic processes. Here, we evaluated the efficacy of 5 (S), 6 (R)-lipoxin A4 methyl ester (LXA4 ME), a stable synthetic analogue of lipoxin A4 in cerebral ischemia reperfusion injury in rats. Transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h. Intracerebroventricular administration of LXA4 ME immediately after onset of ischemia ameliorated neurological dysfunctions, reduced infarction volume and attenuated neuronal apoptosis. Moreover, Treatment with LXA4 ME suppressed neutrophils infiltration and lipid peroxidation levels; inhibited the activation of microglia and astrocytes; reduced the expression of pro-inflammatory cytokines TNF-α and IL-1β; and up-regulated the expression of anti-inflammatory cytokines IL-10 and TGF-β1 in the ischemic brain. In addition, activation of NF-κΒ was inhibited by LXA4 ME treatment. These results demonstrate that treatment of LXA4 ME affords strong neuroprotective effect against cerebral ischemia reperfusion injury, and that these effects might be associated with its anti-inflammatory property.