Protective effect of tetraethyl pyrazine against focal cerebral ischemia/reperfusion injury in rats: therapeutic time window and its mechanism.
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.
Jia
Jie
J
Department of Rehabilitation, Huashan Hospital, and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200040, China.
Zhang
Xi
X
Hu
Yong-Shan
YS
Wu
Yi
Y
Wang
Qing-Zhi
QZ
Li
Na-Na
NN
Wu
Cai-Qin
CQ
Yu
Hui-Xian
HX
Guo
Qing-Chuan
QC
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
D018696:Neuroprotective Agents; D011719:Pyrazines; D013879:Thioredoxins; D054481:Thioredoxin Reductase 1; C516126:Txnrd1 protein, rat; C017953:tetramethylpyrazine