title: Neuroprotective effects of Aceglutamide on motor function in a rat model of cerebral ischemia and reperfusion.
abstract: OBJECTIVE
  To investigate the effect and underlying mechanism of Aceglutamide on motor dysfunction in rats after cerebral ischemia-reperfusion.
  
  
  METHODS
  Adult male Sprague-Dawley rats were subjected to 2 h transient middle cerebral artery occlusion (MCAO). Aceglutamide or vehicle was intraperitoneally given to rats at 24 h after reperfusion and lasted for 14 days. Subsequently functional recovery was assessed and number of tyrosine hydroxylase (TH)-positive neurons in substantia nigra (SN) was analyzed. Tumor necrosis factor receptor-associated factor 1(TRAF1), P-Akt and Bcl-2/Bax were determined in mesencephalic tissue by Western blot method. PC12 cells and primary cultured mesencephalic neurons were employed to further investigate the mechanism of Aceglutamide.
  
  
  RESULTS
  Aceglutamide treatment improved behavioral functions, reduced the infarction volume, and elevated the number of TH-positive neurons in the SN. Moreover, Aceglutamide significantly attenuated neuronal apoptosis in the SN. Meanwhile Aceglutamide treatment significantly inhibited the expression of TRAF1 and up-regulated the expression of P-Akt and Bcl-2/Bax ratio both in vitro and in vivo.
  
  
  CONCLUSIONS
  Aceglutamide ameliorated motor dysfunction and delayed neuronal death in the SN after ischemia, which involved the inhibition of pro-apoptotic factor TRAF1 and activation of Akt/Bcl-2 signaling pathway. These data provided experimental information for applying Aceglutamide to ischemic stroke treatment.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.forename: Chao
authors.initials: C
authors.lastname: Ji
authors.forename: Ji
authors.initials: J
authors.lastname: Zheng
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liang
authors.forename: Chun-Ying
authors.initials: CY
authors.lastname: Hou
authors.forename: Yan-Yong
authors.initials: YY
authors.lastname: Liu
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Zuo
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005973:Glutamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery; D007274:Injections, Intraperitoneal; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009069:Movement Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; C032007:aceglutamide; D005973:Glutamine
keywords: Aceglutamide; TNF receptor associated factor 1 (TRAF1); apoptosis; cerebral ischemia and reperfusion; motor function; neuroprotection; substantia nigra