title: RNA interference-mediated downregulation of Beclin1 attenuates cerebral ischemic injury in rats.
abstract: OBJECTIVE
  To test the role of the Beclin 1-dependent autophagy pathway in brain damage during cerebral ischemia.
  
  
  METHODS
  Focal cerebral ischemia was established in rats using a middle cerebral artery occlusion (MCAO) model. A lentiviral vector-associated RNA interference (RNAi) system was stereotaxically injected into the ipsilateral lateral ventricle to reduce Beclin1 expression. We measured the ipsilateral infarct volume, autophagosome formation, neurogenesis and apoptosis, all of which could be modulated by Beclin1 RNAi.
  
  
  RESULTS
  On the 14th day after MCAO, Beclin1 downregulation by RNAi increased the population of neural progenitor cells (BrdU(+)-DCX(+)), newborn immature cells (BrdU(+)-Tuj-1(+)) and mature neurons (BrdU(+)-MAP-2(+)), and reduced the apoptosis of immature neurons (caspase-3(+)-DCX(+) and caspase-3(+)-Tuj-1(+)) surrounding the ischemic core of the ipsilateral hemisphere. Furthermore, RNAi-mediated downregulation of Beclin1 decreased infarct volume and inhibited histological injury and neurological deficits.
  
  
  CONCLUSIONS
  RNAi-mediated downregulation of Beclin1 improves outcomes after transient MCAO.Acta Pharmacologica Sinica (2009) 30: 919-927; doi: 10.1038/aps.2009.79.
authors: Research Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
authors: Yong-Qiu
authors: YQ
authors: Zheng
authors: Jian-Xun
authors: JX
authors: Liu
authors: Xin-Zhi
authors: XZ
authors: Li
authors: Li
authors: L
authors: Xu
authors: Yong-Gang
authors: YG
authors: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D000071186:Beclin-1; D001522:Behavior, Animal / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D000089662:Doublecortin Protein; D015536:Down-Regulation; D020244:Infarction, Middle Cerebral Artery; D020547:Lateral Ventricles / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C512829:Becn1 protein, rat; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein