Efficacy of the 21-aminosteroid U74006F in improving neurological recovery after spinal cord injury in rats.
The efficacy of three different regimens of the 21-aminosteroid U74006F in counteracting the neurological damage after spinal cord compression causing paraparesis in rats was investigated. Three groups of ten animals each were given totally 6 mg/kg of U74006F in different regimens beginning one hour after injury (A: bolus doses of 1.5 mg/kg at 1, 4, 7 and 10 hours; B: bolus of 1.5 mg/kg at 1 hour and 4.5 mg/kg as an infusion over the next 9 hours; and C: infusion alone, 6 mg/kg, given between 1 and 10 hours after trauma). Two groups of ten animals each received vehicle alone in administration modes comparable to those of the U74006F treated animals. The motor function was assessed daily on the inclined plane. On day one, the capacity angle had decreased from about 62 degrees preoperatively to 28-30 degrees in the two vehicle-treated groups and in group C. In these groups there was a similar improvement in neurological function and on day 9 the capacity angles were 49-55 degrees. In groups A and B, both of which received a bolus dose of U74006F at 1 hour, the neurological outcome improved on day one with capacity angles of 38-40 degrees. The difference in neurological function between the animals given U74006F as bolus doses and those given vehicle alone persisted over the entire observation span until day 9. The data suggest that early treatment with a bolus dose seems to be required in order to obtain an effect of U74006F on neurological recovery.
Department of Neurosurgery, University Hospital, Uppsala, Sweden.
A
A
Holtz
B
B
Gerdin
D000818:Animals; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D011281:Pregnatrienes / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013119:Spinal Cord Injuries / Q000188:drug therapy*
D011281:Pregnatrienes; C053355:tirilazad