Baffour R, Achanta K, Kaufman J, Berman J, Garb J L, Rhee S, Friedmann P
Department of Surgery, Baystate Medical Center, Springfield, Massachusetts, USA.
J Neurosurg. 1995 Jul;83(1):105-10. doi: 10.3171/jns.1995.83.1.0105.
The authors evaluated the effects of exogenous basic fibroblast growth factor (bFGF) in combination with intravenous methylprednisolone on neurological function and cord angiogenesis in a model of spinal cord injury. Cord injury was produced by extradural clip compression through a T-1 laminectomy. Rats were randomized to one of six groups. Group A was given sham laminectomy without cord injury or treatment. The remaining animals were divided into five groups: untreated injury (Group B); injury treated with methylprednisolone (Group C); combined methylprednisolone and 1 microgram bFGF administered locally at the site of injury (Group D); methylprednisolone and 3 micrograms bFGF (Group E); or methylprednisolone and 3 micrograms heated bFGF (Group F). Groups C through F received treatment 1 hour after cord injury. At 1, 2, 3, and 4 weeks after surgery, neurological function of hindlimbs was assessed by blinded observers using an established multiple test method (toe spread, reflexes to extension, pain, and pressure as well as inclined plane and swim test) with tests graded and results expressed as a combined behavioral score. Animals were killed to study spinal cord angiogenesis in cord samples (2-mm sections proximal and distal to the injury site) by capillary density determination. Behavioral scores over time showed a significant difference among Groups B, C, D, E, and F (p = 0.0044), with Groups E and B maintaining highest and lowest scores, respectively. There was a linear dose effect of bFGF over time (p = 0.0187). At 4 weeks, scores showed a difference among the five groups (p = 0.006), with Group E showing higher scores than any other treatment group (for example, vs. group F: p = 0.035). There was a significant difference among the groups in gray matter capillary density counts: proximal (p = 0.0192) and distal (p = 0.024), whereas white matter capillary counts were similar across treatment groups. These results show: 1) possible synergism exists between methylprednisolone and bFGF, such that combinations of these drugs significantly enhance neurological recovery, 2) bFGF exhibits a dose-response effect in function but not in capillary density, and 3) heated, inactivated bFGF is not therapeutically effective.
作者在脊髓损伤模型中评估了外源性碱性成纤维细胞生长因子（bFGF）联合静脉注射甲泼尼龙对神经功能和脊髓血管生成的影响。通过T-1椎板切除术进行硬膜外夹闭压迫来造成脊髓损伤。将大鼠随机分为六组。A组接受假椎板切除术，不造成脊髓损伤也不进行治疗。其余动物分为五组：未治疗的损伤组（B组）；用甲泼尼龙治疗的损伤组（C组）；甲泼尼龙联合1微克bFGF在损伤部位局部给药的组（D组）；甲泼尼龙联合3微克bFGF的组（E组）；或甲泼尼龙联合3微克加热bFGF的组（F组）。C组至F组在脊髓损伤后1小时接受治疗。在术后1、2、3和4周，由不知情的观察者使用既定的多项测试方法（趾展、对伸展、疼痛和压力的反射以及斜面和游泳测试）评估后肢的神经功能，对测试进行评分，并将结果表示为综合行为评分。处死动物，通过测定毛细血管密度来研究脊髓样本（损伤部位近端和远端2毫米切片）中的脊髓血管生成。随时间变化的行为评分显示，B组、C组、D组、E组和F组之间存在显著差异（p = 0.0044），E组和B组分别保持最高和最低评分。bFGF随时间呈现线性剂量效应（p = 0.0187）。在4周时，五组之间的评分存在差异（p = 0.006），E组的评分高于任何其他治疗组（例如，与F组相比：p = 0.035）。各组之间灰质毛细血管密度计数存在显著差异：近端（p = 0.0192）和远端（p = 0.024），而白质毛细血管计数在各治疗组之间相似。这些结果表明：1）甲泼尼龙和bFGF之间可能存在协同作用，使得这些药物的组合显著增强神经恢复；2）bFGF在功能上表现出剂量反应效应，但在毛细血管密度方面没有；3）加热灭活的bFGF没有治疗效果。
