Chondroitinase applied to peripheral nerve repair averts retrograde axonal regeneration
Chondroitinase applied to peripheral nerve repair averts retrograde axonal regeneration
复制标题
DOI：
10.1016/j.expneurol.2006.08.004
复制
发表时间：
2007-01-01
影响因子：
5.3
通讯作者：
Muir, David
中科院分区：
文献类型：
--
作者：
Graham, James B.;Neubauer, Debbie;Muir, David
顺行、靶向轴突再生是神经修复的明确目标。然而，异常和功能失调的再生也很常见。在手术神经接合部位，轴突芽遇到富含抑制生长的硫酸软骨素蛋白聚糖的纤维化结缔组织，这可能导致轴突再生的误导。在本研究中，我们测试了以下假设：通过在神经修复部位应用软骨素酶降解硫酸软骨素蛋白多糖可以减少异常轴突生长。成年大鼠接受双侧坐骨神经横断和端对端修复。一根神经注射软骨素酶 ABC，而对侧神经仅用载体治疗。 28周后，通过对神经内（束内）和神经本身外（束外）的神经丝免疫阳性轴突进行评分来评估修复近端的逆行轴突再生。在对照和软骨素酶治疗条件下，束内逆行轴突生长相同。相比之下，软骨素酶治疗导致束外逆行轴突生长显着减少（93%）。神经轴突出口的减少与顺行再生的增加和运动功能恢复的改善同时发生。基于这些发现，我们得出结论，在神经横断修复部位应用软骨素酶可以避免功能失调的束外逆行轴突生长。 (c) 2006 Elsevier Inc. 保留所有权利。
Antegrade, target-directed axonal regeneration is the explicit goal of nerve repair. However, aberrant and dysfunctional regrowth is commonly observed as well. At the site of surgical nerve coaptation, axonal sprouts encounter fibrotic connective tissue rich in growth-inhibiting chondroitin sulfate proteoglycan that may contribute to misdirection of axonal regrowth. In the present study, we tested the hypothesis that degradation of chondroitin sulfate proteoglycan by application of chondroitinase at the site of nerve repair can decrease aberrant axonal growth. Adult rats received bilateral sciatic nerve transection and end-to-end repair. One nerve was injected with chondroitinase ABC and the contralateral nerve treated with vehicle alone. After 28 weeks, retrograde axonal regeneration was assessed proximal to the repair by scoring neurofilament-immunopositive axons within the nerve (intrafascicular) and outside the nerve proper (extrafascicular). Intrafascicular retrograde axonal growth was equivalent in both control and chondroitinase treatment conditions. In contrast, chondroitinase treatment caused a pronounced (93%) reduction in extrafascicular retrograde axonal growth. The decrease in axon egress from the nerve was coincident with an increase in antegrade regeneration and improved recovery of motor function. Based on these findings, we conclude that chondroitinase applied at the site of nerve transection repair averts dysfunctional extrafascicular retrograde axonal growth. (c) 2006 Elsevier Inc. All rights reserved.