Abstract
The effects of the neuroprotective aminosteroid U74006F (tirilazad mesylate, Freedox) were monitored microdialytically in rat cortex during three 4 h periods beginning immediately, 25 h and 49 h after permanent middle cerebral artery occlusion. Either U74006F or vehicle only was administered 15 min, 2 h, 6 h, 12 h and 24 h after operation. The dialysate was analysed for on-line pH, ascorbic acid, uric acid, glucose and lactate. The efficacy of post-ischaemic treatment was shown by: a) lesion volume 53h after operation was significantly smaller in U74006F-treated animals; b) microdialytic findings were very similar to those found previously with pre-ischaemic drug application (reduction in release of ascorbic acid, uric acid and lactate, increased pH); c) an effect of U74006F on lactate release could still be seen on days 2 and 3; and d) increases in uric acid on days 2 and 3, possibly reflecting delayed cell death, were smaller in aminosteroid treated animals.
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