title: Neuroprotection by manganese superoxide dismutase (MnSOD) mimics: antioxidant effect and oxidative stress regulation in acute experimental stroke.
abstract: OBJECTIVE
  Manganese superoxide dismutase (MnSOD), one of the most crucial antioxidant enzymes in the central nervous system, is thought to be one of the major mechanisms by which cells counteract the injuries of reactive oxygen species after cerebral ischemia. In this study, we used a novel synthesized compound (MnTm4PyP) with highly effective superoxide dismutase activity to study the therapeutic potential of MnSOD and the possible underlying mechanisms in cerebral ischemia.
  
  
  METHODS
  Primary cultured cortical neurons were used to examine the protective effect of the compounds. Mice with middle cerebral artery occlusion were used as ischemic stroke animal model. Animals were pretreated with MnTm4PyP intravenously 30 min before surgery. At 24 h after surgery, neurological behavior and histological function were observed. Infarcted cortex tissues and cultured neurons were collected for investigation of the oxidative stress signaling pathways.
  
  
  RESULTS
  In vitro studies revealed that MnSOD mimic MnTm4PyP pretreatment significantly increased viability of neurons after injury by H(2) O(2) . Intracellular superoxide radical levels were eliminated. In vivo experiments demonstrated MnTm4PyP pretreatment reduced infarct volume and improved neurological function. The MnSOD mimic alleviated oxidative stress and apoptosis.
  
  
  CONCLUSIONS
  MnSOD is an effective therapeutic target in ischemic stroke prevention because of its antioxidant effects and oxidative stress regulation.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Huang
authors.forename: Fei
authors.initials: F
authors.lastname: Guo
authors.forename: Yuan-Zhao
authors.initials: YZ
authors.lastname: Cao
authors.forename: Wen
authors.initials: W
authors.lastname: Shi
authors.forename: Qing
authors.initials: Q
authors.lastname: Xia
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002734:Chlorophyll / Q000737:chemistry / Q000627:therapeutic use*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000150:complications* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009422:Nervous System Diseases / Q000188:drug therapy / Q000209:etiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000502:physiology*; D017601:Oxygen Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C497250:Ddit3 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018696:Neuroprotective Agents; D017601:Oxygen Compounds; D002734:Chlorophyll; D051742:Transcription Factor CHOP; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D002118:Calcium