title: PPARα Agonist Fenofibrate Ameliorates Learning and Memory Deficits in Rats Following Global Cerebral Ischemia.
abstract: Increasing evidence demonstrates that local inflammation contributes to neuronal death following cerebral ischemia. Peroxisome proliferator-activated receptor α (PPARα) activation has been reported to exhibit many pharmacological effects including anti-inflammatory functions. The aim of this study was to investigate the neuroprotective effects of PPARα agonist fenofibrate on the behavioral dysfunction induced by global cerebral ischemia/reperfusion (GCI/R) injury in rats. The present study showed that fenofibrate treatment significantly reduced hippocampal neuronal death, and improved memory impairment and hippocampal neurogenesis after GCI/R. Fenofibrate administration also inhibited GCI/R-induced over-activation of microglia but not astrocytes and prevented up-regulations of pro-inflammatory mediators in hippocampus. Further study demonstrated that treatment with fenofibrate suppressed GCI/R-induced activations of P65 NF-κB and P38 MAPK. Our data suggest that the PPARα agonist fenofibrate can exert functional recovery of memory deficits and neuroprotective effect against GCI/R in rats via triggering of neurogenesis and anti-inflammatory effect mediated by inhibiting activation of P65 NF-κB and P38 MAPK in the hippocampus, which can contribute to improvement in neurological deficits.
authors.affiliation: Department of Anatomy, Guangzhou Medical University, Guangzhou, 510182, Guangdong, China, xag2005@sohu.com.
authors.forename: Ai-Guo
authors.initials: AG
authors.lastname: Xuan
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Da-Hong
authors.initials: DH
authors.lastname: Long
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Ji
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Zhang
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Liu
authors.forename: Le-Peng
authors.initials: LP
authors.lastname: Hong
authors.forename: Xiao-Song
authors.initials: XS
authors.lastname: He
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Chen
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D016923:Cell Death / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000473:pathology; D007249:Inflammation / Q000150:complications / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007858:Learning / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications / Q000473:pathology; D051996:Transcription Factor RelA / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D047493:PPAR alpha; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D048051:p38 Mitogen-Activated Protein Kinases; D011345:Fenofibrate