PPARα Agonist Fenofibrate Ameliorates Learning and Memory Deficits in Rats Following Global Cerebral Ischemia

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• 作者：Ai-Guo Xuan ; Yan Chen ; Da-Hong Long ; Meng Zhang ; Wei-Dong Ji…
• 关键词：Global cerebral ischemia ; PPARα ; Fenofibrate ; Microglia ; P65 NF ; κB ; P38 MAPK
• 刊名：Molecular Neurobiology
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：52
• 期：1
• 页码：601-609
• 全文大小：2,674 KB
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• 作者单位：Ai-Guo Xuan (1)
  Yan Chen (2)
  Da-Hong Long (1)
  Meng Zhang (3)
  Wei-Dong Ji (4)
  Wen-Juan Zhang (5)
  Ji-Hong Liu (6)
  Le-Peng Hong (1)
  Xiao-Song He (1)
  Wen-Liang Chen (7)
  
  1. Department of Anatomy, Guangzhou Medical University, Guangzhou, 510182, Guangdong, China
  2. Respiratory Department, Liwan Hospital of Guangzhou Medical University, Guangzhou, 510170, Guangdong, China
  3. Department of Physiology, Georgia Regents University, Augusta, 30912, GA, USA
  4. Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong, China
  5. School of Public Health, Southern Medical University, Guangzhou, 510515, Guangdong, China
  6. Department of Neurobiology, Southern Medical University, Guangzhou, 510515, Guangdong, China
  7. Department of Pharmacology, Guangzhou Medical University, Guangzhou, 510182, Guangdong, China
  
• 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
• 出版者：Springer US
• ISSN：1559-1182

文摘

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.