Black P, Markowitz R S, Finkelstein S D, McMonagle-Strucko K, Gillespie J A
Department of Neurosurgery, Hahnemann University School of Medicine, Philadelphia, Pennsylvania.
Neurosurgery. 1988 Jan;22(1 Pt 1):61-6. doi: 10.1227/00006123-198801010-00009.
Variable benefits from the use of a number of calcium channel blockers in experimental spinal cord injury have been reported. To our knowledge, these agents have not been previously tested in a contusion model of cord injury in which neurological outcome is one of the critical outcome parameters. We carried out preliminary behavioral toxicity testing to identify a range of low, moderate, and high dosage levels of the calcium channel blocker, nicardipine; these dosage levels were to be used subsequently in formal testing. After laminectomy at T8 under general anesthesia in rats, a 10-g weight was dropped from a height of 5 cm onto the spinal cord. The animals were randomly assigned to four groups: control or one of three nicardipine treatment groups: (a) low dose (1 mg/kg, followed by a continuous 23-hour infusion of 0.5 mg/kg/hour), (b) moderate dose (10 mg/kg, followed by 5 mg/kg/hour for 23 hours, and (c) high dose (20 mg/kg, followed by 23-hour infusion of 10 mg/kg/hour). Functional recovery was tested over the course of 4 weeks with the Tarlov scale, the inclined plane, and a sensory-motor battery of tests (combined behavioral score). After sacrifice at 4 weeks, morphometric analysis of residual gray and white matter was performed at the epicenter of the spinal cord injury. Statistical analysis of the behavioral data failed to reveal any differences among the control or nicardipine treatment groups. The morphometric analysis similarly failed to show differences between the control and any treatment group.(ABSTRACT TRUNCATED AT 250 WORDS)
据报道,在实验性脊髓损伤中使用多种钙通道阻滞剂有不同的效果。据我们所知,这些药物此前尚未在脊髓损伤的挫伤模型中进行测试,而在该模型中,神经学结果是关键的结果参数之一。我们进行了初步的行为毒性测试,以确定钙通道阻滞剂尼卡地平的一系列低、中、高剂量水平;这些剂量水平随后将用于正式测试。在大鼠全身麻醉下进行T8椎板切除术后,将一个10克的重物从5厘米的高度 dropped 到脊髓上。动物被随机分为四组:对照组或三个尼卡地平治疗组之一:(a) 低剂量组(1毫克/千克,随后以0.5毫克/千克/小时的速度持续输注23小时),(b) 中剂量组(10毫克/千克,随后以5毫克/千克/小时的速度输注23小时),以及(c) 高剂量组(20毫克/千克,随后以10毫克/千克/小时的速度输注23小时)。在4周的时间里,使用塔尔洛夫量表、斜面和感觉运动测试电池(综合行为评分)对功能恢复进行测试。在4周后处死动物后,在脊髓损伤的震中对残留的灰质和白质进行形态计量分析。行为数据的统计分析未能揭示对照组或尼卡地平治疗组之间的任何差异。形态计量分析同样未能显示对照组与任何治疗组之间的差异。(摘要截断于250字)