PPAR and Stroke Outcome
We hypothesize that PPARα activation has prophylactic effects in improving stroke outcomes. This hypothesis agrees with one clinical study demonstrating that gemfibrozil, one type of fibrate, had reduced stroke incidence in men with a history of coronary heart disease (Bloomfield Rubins et al., VA-HIT study, 2001). We examined the impact of fibrates on cerebral blood flow in mice subjected to ischemic stroke. We measured cerebral blood flow by laser speckle imaging in mice. This new imaging technique records cerebral blood flow as high resolution image in a real-time and repeated manner. We demonstrated that two fibrates, fenofibrate and gemfibrozil, improved cerebral blood flow in mice after ischemic stroke. Our recent preliminary study suggests that fenofibrate elevates superoxide dismutase levels, with a preference in the extracellular isoform, in mouse cerebral microvessels. This action may underlie the beneficial cerebrovascular effects of fibrates in mice.