Effect of Delayed Administration of U74006F (Tirilazad Mesylate) on Recovery of Locomotor Function After Experimental Spinal Cord Injury
Effect of Delayed Administration of U74006F (Tirilazad Mesylate) on Recovery of Locomotor Function After Experimental Spinal Cord Injury
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DOI：
10.1089/neu.1991.8.187
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发表时间：
1991-09-01
影响因子：
4.2
通讯作者：
Means, Eugene D.
中科院分区：
文献类型：
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作者：
Anderson, Douglas K.;Hall, Edward D.;Means, Eugene D.
从180g压迫猫L2脊髓5分钟后的30分钟、2小时、4小时或8小时开始，开始输注U74006F。在这个系列中，猫接受U74006F的总剂量为5 mg/kg/48小时。另一组受伤猫在伤后8小时接受U74006F三倍剂量的治疗(即48小时总剂量为15 mg/kg)。对照组在48小时内接受等量的赋形剂(柠檬酸盐缓冲液)。研究人员在不知道所用材料的时间和类型(即车辆或药物)的情况下，每周评估一次猫的地面活动恢复情况，为期4周，评分为11分。伤后4周，应用U74006F的猫在伤后30分钟、2小时、4小时和8小时的运动恢复无显著差异。然而，只有在伤后30分钟、2小时或4小时治疗的组的恢复显著高于使用车辆治疗的对照组。猫在伤后8h接受U74006F 5 mg/kg/48h和15 mg/kg/48hU74006F治疗，其运动功能与赋形剂治疗组无显著差异。在伤后30分钟、2小时、4小时或8小时接受5 mg/kg/48小时剂量治疗的猫，4周平均(+/-)恢复评分分别为6.8+/-0.9、5.9+/-1.0、7.2+/-1.1和4.7+/-2.9。伤后8小时给予15 mg/kg/48小时剂量治疗的猫的平均康复评分为3.4+/-1.8。接受车辆治疗的对照组的平均得分为1.8+/-0.8。这些发现表明，在我们的压迫脊髓损伤模型中，U74006F可以显着保护运动功能，如果在损伤后4小时使用。将该化合物的给药推迟到受伤后8小时，即使剂量增加三倍，也会导致其保护能力的严重丧失。
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.