Protective effect of tetraethyl pyrazine against focal cerebral ischemia/reperfusion injury in rats: Therapeutic time window and its mechanism

Department of Rehabilitation, Huashan Hospital, and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200040, China.
Thrombosis Research (Impact Factor: 2.45). 02/2009; 123(5):727-30. DOI: 10.1016/j.thromres.2008.11.004
Source: PubMed


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.
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.
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.
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.

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    • "The decrease of Trx expression indicates a decline in anti-oxidative ability and spermatogenesis. A previous study demonstrated that the expression of thioredoxin-1 and thioredoxin-2 was significantly decreased in cerebrums of rats with ischemia and reperfusion injury [19]. During ischemia and reperfusion injury, excessive radical production is produced and leads to protein oxidation and DNA damage [17]. "
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