Chronic effects of an aminosteroid on microdialytically measured parameters after experimental middle cerebral artery occlusion in the rat

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 alter 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 53 h 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.