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 4h periods beginning immediately, 25h and 49h after permanent middle cerebral artery occlusion. Either U74006F or vehicle only was administered 15 min, 2h, 6h, 12h and 24h 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.
Alessandri
B
B
Department of Research, Cantonal Hospital, Basel, Switzerland. Balessan@hsc.vcu.edu
Basciani
R
R
Langemann
H
H
Lyrer
P
P
Pluess
D
D
Landolt
H
H
Gratz
O
O
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005609:Free Radicals / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011281:Pregnatrienes / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D014527:Uric Acid / Q000378:metabolism
D005609:Free Radicals; D018696:Neuroprotective Agents; D011281:Pregnatrienes; D014527:Uric Acid; D019344:Lactic Acid; D005947:Glucose; D001205:Ascorbic Acid; C053355:tirilazad