Neuroprotective Effects of Chronic Fenofibrate Treatment via Modulating the Immunoreactivity of Cleaved Caspase-3 in Stroke Induced by Transient Middle Cerebral Artery Occlusion Rat Model

Özet

AIm: Current stroke therapies include lipid-lowering drugs, which reduce inflammation and serve to stabilize the atherosclerotic plaque to demonstrate better outcome and neuroprotection. Peroxisome proliferator activated receptors (PPAR) α regulates lipid homeostasis and is a target of fibrates, which have a neuroprotective function by various mechanisms. In this study, we aimed to evaluate the role of the PPARα agonist, fenofibrate, in the modulation of cleaved caspase-3 immunoreactivity and at the final infarct volume in an experimental ischemia/reperfusion rat model by induced transient proximal middle cerebral artery occlusion. mATERIAl and mEThODS: A total of 65 male Sprague Dawley rats were allocated into 4 groups; sham (n =5), experiment 1 (n=20), experiment 2 (n=20), experiment 3 (n=20). All experiment groups were divided to 3 subgroups in order to evaluate the final infarct volume at 24th hour (n=5) and the immunoreactivity of cleaved caspase -3 at different time periods [at first hour (n=5), at 6th hour (n=5), at 24th hour (n=5)] after transient middle cerebral artery occlusion (MCAo). At the study, the experiment groups (Experiment 1 and Experiment 2) were received the fenofibrate-diet during 14 days before ischemia procedure. All animals were sacrificed at 24thhours after MCAo. Infarction volumes were calculated from 2,3,5,triphenyltetrozolium chloride (TTC)- stained brain sections. RESUlTS: We found that fenofibrate-therapy reduced significantly more body weight than the other experiment groups (p<0.05). At the time intervals, a decrease of immunoreactivity of cleaved caspase-3 was significantly observed with fenofibrate therapy after MCAo (p<0.05). Chronic fenofibrate treatment before cerebral ischemia significantly reduced the infarction size after MCAo compared with the other groups (respectively; p = 0.011 and p< 0.000). CONClUSION: Fenofibrate treatment has neuroprotective effects on middle cerebral artery infarcts