title: Both endoplasmic reticulum and mitochondrial pathways are involved in oligodendrocyte apoptosis induced by capsular hemorrhage.
abstract: OBJECTIVE
  The white matter injury caused by intracerebral hemorrhage (ICH) includes demyelination and axonal injury. Oligodendrocyte apoptosis is reported to be involved in triggering demyelination. Experimental observations indicate that both endoplasmic reticulum and mitochondrial pathways could mediate cell apoptosis. The purpose of this study was to investigate the demyelination and the possible mechanisms in an autologous blood-injected rat model of internal capsule hemorrhage.
  
  
  METHODS
  Transmission electron microscope was applied to examine the pathological changes of myelinated nerve fibers in internal capsule. Western blotting was used to detect the myelin basic protein (MBP) which was an important component of myelin sheath. Double immunofluorescence and Western blotting were used to determine the apoptosis and apoptotic pathways. The levels of caspase-12 (a representative protein of endoplasmic reticulum stress) and cytochrome c (an apoptosis factor released from mitochondria) were assessed in this study.
  
  
  RESULTS
  Demyelination occurred on day 1, 3, and 7 after ICH onset. Myelin sheaths of internal capsule nerve fibers were swollen and broken down in ICH groups. MBP expression showed a downregulation after ICH with its minimum value occurred on day 7 post-ICH. Besides, neuron and oligodendrocyte apoptosis were observed at different time intervals post-ICH accompanied with an upregulated caspase-12 expression and enhanced cytochrome c release.
  
  
  CONCLUSIONS
  These results suggested that oligodendrocyte and neuron apoptosis may contribute to the demyelination induced by internal capsule hemorrhage and oligodendrocyte apoptosis is positively mediated through both endoplasmic reticulum and mitochondrial pathways.
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhuo
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, People's Republic of China.
authors.forename: GuoPing
authors.initials: G
authors.lastname: Qiu
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, People's Republic of China.
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, People's Republic of China.
authors.forename: KeJian
authors.initials: K
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Huang
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, People's Republic of China.
authors.forename: WeiTian
authors.initials: W
authors.lastname: Lu
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, People's Republic of China.
authors.forename: ShiYe
authors.initials: S
authors.lastname: Xu
authors.affiliation: Traditional Chinese Medical College, Chongqing Medical University, Chongqing 400016, People's Republic of China.
authors.forename: SiQin
authors.initials: S
authors.lastname: Huang
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, People's Republic of China. Electronic address: Sunsq2151@cqmu.edu.cn.
authors.forename: ShanQuan
authors.initials: S
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis; D002543:Cerebral Hemorrhage / Q000378:metabolism* / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D020772:Internal Capsule / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism / Q000648:ultrastructure; D009836:Oligodendroglia / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: Apoptosis; Demyelination; Intracerebral hemorrhage; Oligodendrocyte