title: Blocking weight-induced spinal cord injury in rats: therapeutic effect of the 21-aminosteroid U74006F.
abstract: The effect of the 21-aminosteroid U74006F on neurologic recovery after a spinal cord compression trauma was investigated in rats. The compression was induced by a blocking weight technique, in which a 35 g (moderate injury) or a 50 g (severe injury) weight was applied for 5 minutes to an 11 mm2 plate over the midthoracic spinal cord. One hour after trauma, the severely injured animals were treated either with U74006F, 3 mg/kg, methylprednisolone, 30 mg/kg, or vehicle, whereas the moderately injured animals received U74006F, 3 mg/kg or vehicle. Neurologic hind limb function was evaluated by the inclined plane technique. On day 1 after trauma, subtotal paraparesis occurred in the 35 g group treated with vehicle (31 +/- 1 degrees, mean +/- SEM) on the inclined plane vs 64 +/- 1 degrees before trauma) and complete paraplegia in the 50 g group (22 +/- 1 degrees). Treatment with U74006F resulted in less hind limb weakness in the 35 g group (42 +/- 2 degrees) but had no beneficial effect in the 50 g group (25 +/- 2 degrees). Neurologic function gradually improved in the 35 g groups over the 9-day observation period. However, those animals treated with U74006F were significantly better over the entire period. In the 50 g group, no recovery from paraplegia was noted over the 4 day observation period in any of the three groups. These results suggest that after weight-induced spinal cord trauma, U74006F is associated with improved neurologic function in moderately injured, but not severely injured animals.
authors.affiliation: Department of Neurosurgery, University Hospital, Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Holtz
authors.forename: B
authors.initials: B
authors.lastname: Gerdin
mesh_terms: D000818:Animals; D006614:Hindlimb / Q000502:physiology; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors*; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D010264:Paraplegia / Q000503:physiopathology; D011281:Pregnatrienes / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013117:Spinal Cord Compression / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D008054:Lipid Peroxides; D011281:Pregnatrienes; D008775:Methylprednisolone; C053355:tirilazad