Simultaneous treatment with BDNF and CNTF after peripheral nerve transection and repair enhances rate of functional recovery compared with BDNF treatment alone

Simultaneous treatment with BDNF and CNTF after peripheral nerve transection and repair enhances rate of functional recovery compared with BDNF treatment alone
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DOI:
10.1097/00005537-199707000-00029
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发表时间:
1997-07-01
期刊:
影响因子:
2.6
通讯作者:
Terris, DJ
Terris, DJ
中科院分区:
医学2区
文献类型:
--
作者:
Lewin, SL;Utley, DS;Terris, DJ

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目的是研究脑源性神经营养因子(BDNF)和睫状神经营养因子(CNTF)对周围神经再生的影响。 30 只 Sprague-Dawley 大鼠根据三个实验组接受左坐骨神经横断和修复:神经外膜接合(EC)、通过渗透泵输送 BDNF 的 EC(EC-BDNF)、以及以类似方式输送 BDNF 和 CNTF 的 EC(EC-BDNF/CNTF)。使用坐骨功能指数、定量组织形态学和与神经再生相关的蛋白质的分子分析来评估神经再生。在每个时间点比较所有组的方差分析 (ANOVA) 表明,第 20 天、30 天、40 天、50 天、60 天和 80 天各组之间存在显着差异。配对双尾学生 t 检验与 Bonferroni 校正进行多重比较表明,术后 40 天,EC-BDNF/CNTF 组 (n = 7) 的动物与 EC 组 (n = 9)和 EC-BDNF 组(n = 9)(分别为 P < 0.001 和 P < 0.05)。 80 天时,EC-BDNF(P < 0.01)和 EC-BDNF/CNTF(P < 0.05)组的动物与 EC 组相比均表现出更好的功能恢复,并且两个因素组在终点时没有显着差异。形态计量学分析表明,与EC(近端:P < 0.001,远端:P < 0.05)和EC-BDNF(近端:P < 0.01)组相比,EC-BDNF/CNTF组动物的神经具有最大的平均轴突直径,但神经横截面积无显着差异。在远端神经节段中,蛋白质印迹分析显示,EC 组髓磷脂相关糖蛋白的表达高于对照,而 EC-BDNF 和 EC-BDNF/CNTF 组均低于对照。我们得出的结论是,与单独使用 BDNF 治疗相比,BDNF/CNTF 联合治疗提高了功能性坐骨神经再生的早期率,尽管在实验结束时最大恢复程度相似。
The objective was to investigate the effects of brain-derived neurotropic factor (BDNF) and ciliary neurotropic factor (CNTF) on peripheral nerve regeneration. Thirty Sprague-Dawley rats underwent left sciatic nerve transection and repair according to three experimental groups: epineurial coaptation (EC), EC with BDNF delivered by an osmotic pump (EC-BDNF), and EC with BDNF and CNTF delivered similarly (EC-BDNF/CNTF). Nerve regeneration was assessed using sciatic functional indices, quantitative histomorphology, and molecular analysis for proteins associated with nerve regeneration. Analysis of variance (ANOVA) comparing all groups at each time point demonstrated significant differences between groups on days 20, 30, 40, 50, 60, and 80. A paired, two-tailed Student's t-test with the Bonferroni correction for multiple comparisons demonstrated that at 40 days postoperatively, animals in the EC-BDNF/CNTF group (n = 7) manifested superior functional recovery compared with those in the EC group (n = 9) and those in the EC-BDNF group (n = 9) (P < 0.001 and P < 0.05, respectively). At 80 days, the animals in both the EC-BDNF (P < 0.01) and EC-BDNF/CNTF (P < 0.05) groups demonstrated greater functional recovery compared with those in the EC group, with no significant difference between the two factor groups at the endpoint. Morphometric analysis demonstrated that nerves from animals in the EC-BDNF/CNTF group had the largest mean axon diameters as compared with those from the EC (proximal: P < 0.001, distal: P < 0.05) and EC-BDNF (proximal: P < 0.01) groups, No significant differences were seen in nerve cross-sectional area. In distal nerve segments, Western blot analysis revealed that expression of myelin-associated glycoprotein was higher than control for the EC group and lower than control for both the EC-BDNF and EC-BDNF/CNTF groups. We conclude that BDNF/CNTF combined treatment increases the early rate of functional sciatic nerve regeneration over treatment with BDNF alone, although the degree of maximal recovery was similar at the conclusion of the experiment.