Lee Yu-Shang, Lin Ching-Yi, Robertson Richard T, Hsiao Ian, Lin Vernon W
Department of Anatomy, College of Medicine, University of California, Irvine, Irvine, California, USA.
J Neuropathol Exp Neurol. 2004 Mar;63(3):233-45. doi: 10.1093/jnen/63.3.223-a.
Behavioral assessments of hindlimb motor recovery and anatomical assessments of extended axons of long spinal tracts were conducted in adult rats following complete spinal cord transection. Rats were randomly divided into 3 groups: 1) sham control group (laminectomy only; n = 12); 2) transection-only group, spinal cord transection at T8 (n = 20); and 3) experimental treatment group, spinal cord transection at T8, with peripheral nerve grafts (PNG) and application of acidic fibroblast growth factor (aFGF) (n = 14). The locomotor behavior and stepping of all rats were analyzed over a 6-month survival time using the Basso, Beattie, Bresnahan (BBB) open field locomotor test and the contact placing test. Immunohistochemistry for serotonin (5-HT), anterograde tracing with biotinylated dextran amine (BDA), and retrograde tracing with fluoro-gold were used to evaluate the presence of axons below the damage site following treatment. When compared with the transection-only group, the nerve graft with the aFGF group showed 1) significant improvement in hindlimb locomotion and stepping, 2) the presence of 5-HT-labeled axons below the lesion site at lumbar cord level (these were interpreted as regenerated axons from the raphe nuclei), 3) the presence of anterograde BDA labeling of corticospinal tract axons at the graft site and below, and 4) fluoro-gold retrograde labeling of neuron populations in motor cortex and in red nucleus, reticulospinal nuclei, raphe nuclei, and vestibular nuclei. We conclude that peripheral nerve grafts and aFGF treatments facilitate the regrowth of the spinal axons and improve hindlimb function in a T-8 spinal cord-transected rat model.
在成年大鼠完全脊髓横断后，对其进行后肢运动恢复的行为学评估以及长脊髓束延长轴突的解剖学评估。大鼠被随机分为3组：1）假手术对照组（仅行椎板切除术；n = 12）；2）仅横断组，在T8水平进行脊髓横断（n = 20）；3）实验治疗组，在T8水平进行脊髓横断，同时进行周围神经移植（PNG）并应用酸性成纤维细胞生长因子（aFGF）（n = 14）。在6个月的存活期内，使用Basso、Beattie、Bresnahan（BBB）旷场运动试验和接触放置试验分析所有大鼠的运动行为和步态。采用血清素（5-HT）免疫组织化学、生物素化葡聚糖胺（BDA）顺行示踪以及荧光金逆行示踪来评估治疗后损伤部位以下轴突的存在情况。与仅横断组相比，aFGF神经移植组表现为：1）后肢运动和步态显著改善；2）在腰髓水平损伤部位以下存在5-HT标记的轴突（这些被解释为来自中缝核的再生轴突）；3）在移植部位及以下存在皮质脊髓束轴突的BDA顺行标记；4）运动皮层、红核、网状脊髓核、中缝核和前庭核中神经元群体的荧光金逆行标记。我们得出结论，周围神经移植和aFGF治疗可促进脊髓轴突的再生，并改善T-8脊髓横断大鼠模型的后肢功能。
