title: 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.
abstract: OBJECTIVE
  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) ? 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 PPAR? 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.
  
  
  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 24th hours 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).
  
  
  CONCLUSIONS
  Fenofibrate treatment has neuroprotective effects on middle cerebral artery infarcts.
authors: Bor State Hospital, Neurology Clinic, Nigde, Turkey.
authors: Ozge
authors: O
authors: Altintas
authors: Mehmet Ozgen
authors: MO
authors: Altintas
authors: Mehmet Serif
authors: MS
authors: Aydin
authors: Oguz
authors: O
authors: Baran
authors: Veysel
authors: V
authors: Antar
authors: Mukaddes
authors: M
authors: Esrefoglu
authors: Talip
authors: T
authors: Asil
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism*; D061945:Caspase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D011345:Fenofibrate / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D020521:Stroke / Q000188:drug therapy
chemical_list: D061945:Caspase Inhibitors; D018696:Neuroprotective Agents; D053148:Caspase 3; D011345:Fenofibrate