Therapeutic time window and mechanism of tetramethylpyrazine on transient focal cerebral ischemia/reperfusion injury in rats

The purpose of this study was to explore the therapeutic time window and mechanism of tetramethylpyrazine on transient focal cerebral ischemia/reperfusion injury. Middle cerebral artery occlusion was conducted in male Sprague-Dawley rats and 20 mg/kg tetra methyl pyrazine was injected intraperitoneally at different time points. Neurological deficit scores and brain infarction volumes were measured 72 h after reperfusion started. The expression of thioredoxin and thioredoxin reductase were examined at 6 h and at 24 h after reperfusion. Our results included the findings of a significant reduction in neurological deficit scores and infarction volume in the treatment group as compared to the control group. Ischemia/reperfusion injury resulted in a decrease in the expression of thioredoxin, while tetramethylpyrazine administration greatly elevated the expression of thioredoxin-1/thioredoxin-2 mRNA and thioredoxin reductase-1/thioredoxin reductase-2mRNA. These findings suggest that administration of tetra methyl pyrazine, within a 4 h time period post-transient focal stroke, may reduce cerebral ischemic reperfusion damage. Moreover, the neuroprotective effect of tetramethylpyrazine may be mediated, in part, by an increase in genetic transcription of thioredoxin. (C) 2008 Published by Elsevier Ireland Ltd.