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 A(4) methyl ester (LXA(4) ME), a stable synthetic analogue of lipoxin A(4) in cerebral ischemia reperfusion injury in rats. Transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 2h. Intracerebroventricular administration of LXA(4) ME immediately after onset of ischemia ameliorated neurological dysfunctions, reduced infarction volume and attenuated neuronal Apoptosis. Moreover, Treatment with LXA(4) ME suppressed neutrophils infiltration and lipid peroxidation levels; inhibited the activation of microglia and astrocytes; reduced the expression of pro-inflammatory cytokines TNF-alpha and IL-1beta; and up-regulated the expression of anti-inflammatory cytokines IL-10 and TGF-beta1 in the ischemic brain. In addition, activation of NF-kappaBeta was inhibited by LXA(4) ME treatment. These results demonstrate that treatment of LXA(4) ME affords strong neuroprotective effect against cerebral ischemia reperfusion injury, and that these effects might be associated with its anti-inflammatory property.