We previously reported that PPARα activators improved blood circulation in the cerebral cortex after focal ischemia/reperfusion (Guo et al., 2009; 2010). The cortical area into which LPS was injected corresponds to the so-called ischemic penumbra in middle cerebral artery occlusion models which are frequently used to mimic ischemic stroke in humans. In the penumbra, brain inflammation is pronounced. In addition, therapeutic improvement in microcirculation is more pronounced in the penumbra. Therefore, Wy-14643 and fenofibrate may improve penumbral circulation by preventing adhesion of leukocytes and platelets to the endothelial surface, at least in part. Consistent with this notion, fenofibrate has been shown to inhibit ICAM-1 immunoreactivity in the brain after ischemic stroke (Deplanque et al., 2003; Ouk et al., 2009).
