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 cerebra l 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 po st-ischaemic treatment was shown by: a) lesion volume 53 h after operation was significantly smaller in U74006F-treated animals; b) microdialytic find ings were very similar to those found previously with pre-ischaemic drug ap plication (reduction in release of ascorbic acid, uric acid and lactate, in creased 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 r eflecting delayed cell death, were smaller in aminosteroid treated animals.