title: Protective effects of PGC-1α via the mitochondrial pathway in rat brains after intracerebral hemorrhage.
abstract: Peroxisome-proliferator-activated receptor co-activator-1α (PGC-1α) is a transcriptional co-activator that coordinately regulates genes required for mitochondrial biogenesis, which stimulates mitochondrial activity. It is also a major factor in the up-regulation of antioxidant activities that are a response to oxidative stress. However, the role of PGC-1α after intracerebral hemorrhage (ICH) has not been studied. The purpose of the present work was to investigate the effects and mechanism of PGC-1α after ICH in the brain. Brain injury was induced by injecting autologous arterial blood (50μL) into the rat brain. PGC-1α siRNAs were injected into rat brains 24h prior to ICH. Then, 72h after ICH, brains were collected for investigation. Post-assessment included western blot analysis, RT-PCR assay, neurobehavioral function testing, measurement of brain water content, high-performance liquid chromatography (HPLC), and projection electron microscopy on ICH rat models. The concentration of PGC-1α was higher in the ipsilateral striatum after ICH, peaking around 72h after ICH. The expression of NRF-1, TFAM, SOD2, UCP2, mitochondrial DNA, ATP concentration, mitochondrial quantity, and brain water content were increased 72h after ICH. However, the neurological score was decreased 72h after ICH. Treatment with PGC-1α siRNAs significantly decreased the neurological score, ATP concentration, number of mitochondria, expression of NRF-1, TFAM, SOD2, UCP2, and mitochondrial DNA, and increased brain water content and formation of mitochondrial myelin layer structures. In conclusion, our data suggest that PGC-1α protects rat brains via a mitochondrial pathway following ICH.
  
  
  
  PGC-1α intracerebral hemorrhage(ICH); mitochondrial; neuroprotection.
authors.affiliation: Department of Pathology, Chongqing Medical University, Chongqing, People's Republic of China; Institute of Neuroscience, Chongqing Medical University, Chongqing, People's Republic of China; Key Laboratory of Neurobiology, Chongqing Medical University, 400016 Chongqing, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: You
authors.affiliation: Department of Pathology, Chongqing Medical University, Chongqing, People's Republic of China; Institute of Neuroscience, Chongqing Medical University, Chongqing, People's Republic of China; Key Laboratory of Neurobiology, Chongqing Medical University, 400016 Chongqing, People's Republic of China.
authors.forename: Yanghao
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Neurosurgery, The Children's Hospital of Chongqing Medical University, People's Republic of China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhai
authors.affiliation: Department of Pathology, Chongqing Medical University, Chongqing, People's Republic of China; Institute of Neuroscience, Chongqing Medical University, Chongqing, People's Republic of China; Key Laboratory of Neurobiology, Chongqing Medical University, 400016 Chongqing, People's Republic of China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pathology, Chongqing Medical University, Chongqing, People's Republic of China; Institute of Neuroscience, Chongqing Medical University, Chongqing, People's Republic of China; Key Laboratory of Neurobiology, Chongqing Medical University, 400016 Chongqing, People's Republic of China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathology, Chongqing Medical University, Chongqing, People's Republic of China; Institute of Neuroscience, Chongqing Medical University, Chongqing, People's Republic of China; Key Laboratory of Neurobiology, Chongqing Medical University, 400016 Chongqing, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Chongqing Medical University, Chongqing, People's Republic of China; Institute of Neuroscience, Chongqing Medical University, Chongqing, People's Republic of China; Key Laboratory of Neurobiology, Chongqing Medical University, 400016 Chongqing, People's Republic of China. Electronic address: zjbingsheng@sina.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002543:Cerebral Hemorrhage / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D000255:Adenosine Triphosphate
keywords: Intracerebral hemorrhage (ICH); Mitochondrial; Neuroprotection; PGC-1α