title: Protective effect of tetraethyl pyrazine against focal cerebral ischemia/reperfusion injury in rats: therapeutic time window and its mechanism.
abstract: BACKGROUND
  Tetramethyl pyrazine has been considered an effective agent in treating neurons ischemia/reperfusion injury, but the mechanism of its therapeutic effect remains unclear. This study was to explore the therapeutic time window and mechanism of tetramethyl pyrazine on temporary focal cerebral ischemia/reperfusion injury.
  
  
  METHODS
  Middle cerebral artery occlusion was conducted in male Sprague-Dawley rats and 20 mg/kg of tetramethyl pyrazine was intraperitoneally injected at different time points. At 72 h after reperfusion, all animals' neurologic deficit scores were evaluated. Cerebrums were removed and cerebral infarction volume was measured. The expression of thioredoxin and thioredoxin reductase mRNA was determined at 6 and 24 h after reperfusion.
  
  
  RESULTS
  Cerebral infarction volume and neurological deficit scores were significantly decreased in the group with tetramethyl pyrazine treatment. The expression of thioredoxin-1/thioredoxin-2 and thioredoxin reductase-1/thioredoxin reductase-2 was significantly decreased in rats with ischemia/reperfusion injury, while it was increased by tetramethyl pyrazine administration.
  
  
  CONCLUSIONS
  Treatment with tetramethyl pyrazine, within 4 h after reperfusion, protects the brain from ischemic reperfusion injury in rats. The neuroprotective mechanism of tetramethyl pyrazine treatment is, in part, mediated through the upregulation of thioredoxin transcription.
authors.affiliation: Department of Rehabilitation, Huashan Hospital, and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200040, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jia
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.forename: Yong-Shan
authors.initials: YS
authors.lastname: Hu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wu
authors.forename: Qing-Zhi
authors.initials: QZ
authors.lastname: Wang
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Li
authors.forename: Cai-Qin
authors.initials: CQ
authors.lastname: Wu
authors.forename: Hui-Xian
authors.initials: HX
authors.lastname: Yu
authors.forename: Qing-Chuan
authors.initials: QC
authors.lastname: Guo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D054481:Thioredoxin Reductase 1 / Q000502:physiology; D013879:Thioredoxins / Q000502:physiology
chemical_list: D018696:Neuroprotective Agents; D011719:Pyrazines; D013879:Thioredoxins; D054481:Thioredoxin Reductase 1; C516126:Txnrd1 protein, rat; C017953:tetramethylpyrazine