Imamura H, Tator C H
Canadian Paraplegic Association Spinal Cord Research Laboratory, Division of Neurosurgery, Toronto, Ontario, Canada.
Spinal Cord. 1998 Jul;36(7):497-506. doi: 10.1038/sj.sc.3100662.
A method was developed for administering intrathecal pharmacotherapy in a rat model of spinal cord injury. The effects of intrathecal administration of nimodipine on spinal cord blood flow (SCBF) and evoked potentials (EPs) were measured in the normal and injured spinal cord. It had previously been shown that systemic nimodipine caused severe hypotension after spinal cord injury. After baseline SCBF and EPs, 15 uninjured rats were blindly allocated to one of three groups: one placebo group (n = 5); and two groups with intrathecal nimodipine, 0.05 mg/kg (n = 5), or 0.2 mg/kg (n = 5). Ten other rats received a 35 g acute clip compression injury of the spinal cord for 1 minute and, were allocated to one of two groups: placebo (n = 5); and intrathecal nimodipine 0.05 mg/kg (n = 5) given 60 min after injury. In the uninjured groups, neither 0.05 nor 0.2 mg/kg of nimodipine increased SCBF during, or 30 min after, intrathecal infusion. However, the mean arterial blood pressure (MABP) decreased significantly to 69.73.1% after the infusion of 0.2 mg/kg nimodipine and did not recover by 98 min. In all three groups of uninjured rats, the amplitude of the cerebellar EP was decreased 30 min after infusion. After spinal cord injury, there were significant decreases in MABP, SCBF and EP amplitude in both placebo and treatment groups, but there was no therapeutic benefit from nimodipine. Thus, intrathecal infusion of nimodipine did not prevent the hypotension encountered with systemic administration and exerted no beneficial effect on SCBF or EPs after acute spinal cord injury.
已开发出一种在脊髓损伤大鼠模型中进行鞘内药物治疗的方法。在正常和损伤的脊髓中测量了鞘内注射尼莫地平对脊髓血流量（SCBF）和诱发电位（EPs）的影响。此前已表明，全身应用尼莫地平会在脊髓损伤后导致严重低血压。在记录基线SCBF和EPs后，将15只未受伤的大鼠随机分为三组之一：一个安慰剂组（n = 5）；以及两组鞘内注射尼莫地平，剂量分别为0.05 mg/kg（n = 5）或0.2 mg/kg（n = 5）。另外10只大鼠接受了35 g急性夹闭压迫脊髓损伤1分钟，并被分为两组之一：安慰剂组（n = 5）；以及损伤后60分钟给予鞘内尼莫地平0.05 mg/kg（n = 5）。在未受伤组中，鞘内注射期间或注射后30分钟，0.05 mg/kg和0.2 mg/kg的尼莫地平均未增加SCBF。然而，注射0.2 mg/kg尼莫地平后，平均动脉血压（MABP）显著下降至69.7±3.1%，且在98分钟内未恢复。在所有三组未受伤大鼠中，注射后30分钟小脑EP的振幅均降低。脊髓损伤后，安慰剂组和治疗组的MABP、SCBF和EP振幅均显著降低，但尼莫地平没有治疗益处。因此，鞘内注射尼莫地平不能预防全身给药时出现的低血压，对急性脊髓损伤后的SCBF或EPs也没有有益作用。
