Effect of Delayed Administration of U74006F (Tirilazad Mesylate) on Recovery of Locomotor Function After Experimental Spinal Cord Injury

Douglas K. Anderson, Edward D. Hall, J. Mark Braughler, John M. McCall, Eugene D. Means

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Beginning at either 30 minutes, 2 hours, 4 hours, or 8 hours after 180 g compression of the cat L2 spinal cord for 5 minutes, infusion of U74006F was initiated. In this series, the cats received a total U74006F dose of 5 mg/kg/48 hours. An additional group of injured cats was treated at 8 hours postinjury with a three-fold higher dose of U74006F (i.e., a total 48-hour dose of 15 mg/kg). Controls received an equal volume of vehicle (citrate-buffered saline) delivered over 48 hours. The cats were evaluated weekly for 4 weeks for recovery of overground locomotion based on an 11-point scale by an investigator blinded to the time and type (i.e., vehicle or drug) of material administered. By 4 weeks postinjury, there was no significant difference in the locomotor recovery of cats that received U74006F at either 30 minutes, 2 hours, 4 hours, or 8 hours after injury. However, only recovery in the groups treated at 30 minutes, 2 hours, or 4 hours after injury was significantly greater than vehicle-treated controls. Locomotor function in cats receiving either 5 mg/kg/48 hours or 15 mg/kg/48 hours of U74006F at 8 hours postinjury was not significantly different from that of the vehicle-treated animals. Mean (± SEM) 4-week recovery scores were 6.8 ± 0.9, 5.9 ± 1.0, 7.2 ± 1.1, and 4.7 ± 2.9 out of 11 for cats treated at 30 minutes, 2 hours, 4 hours, or 8 hours postinjury, respectively, with the 5 mg/kg/48 hour dose. The mean recovery score for cats treated at 8 hours after injury with the 15 mg/kg/48 hour dose was 3.4 ± 1.8. The average score for the vehicle-treated controls was 1.8 ± 0.8. These findings demonstrate that U74006F can significantly protect locomotor function in our model of compression spinal cord injury if administered as late as 4 hours postinjury. Delaying administration of the compound to 8 hours after injury results in considerable loss of its protective capabilities even if the dose is increased threefold.

Original languageEnglish
Pages (from-to)187-192
Number of pages6
JournalJournal of Neurotrauma
Volume8
Issue number3
DOIs
StatePublished - 1991

ASJC Scopus subject areas

  • Clinical Neurology

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