Combining an autologous peripheral nervous system "bridge" and matrix modification by chondroitinase allows robust, functional regeneration beyond a hemisection lesion of the adult rat spinal cord
Combining an autologous peripheral nervous system "bridge" and matrix modification by chondroitinase allows robust, functional regeneration beyond a hemisection lesion of the adult rat spinal cord
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DOI：
10.1523/jneurosci.1166-06.2006
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发表时间：
2006-07-12
影响因子：
5.3
通讯作者：
Silver, Jerry
中科院分区：
文献类型：
--
作者：
Houle, John D.;Tom, Veronica J.;Silver, Jerry
将软骨素酶ABC（ChABC）应用于成年大鼠脊髓的颈5级（C5）背象限抽吸腔，以降解抑制性硫酸软骨素蛋白多糖的局部积累。其目的是增强再生轴突从周围神经（PN）移植物远端返回C5脊髓的延伸，绕过C3处的半切损伤。ChABC处理的大鼠表现出（1）在运动期间前肢摆动范围的逐渐改善，一些动物进展到将其前肢抬高到鼻子以上的程度，（2）在圆筒测试中使用前肢的能力增强，以及（3）在水平绳索上的平衡和承重改善。切断再生轴突的PN移植物的横切，大大减少了这些功能的改善。PN移植物的轴突再生与行为评估相关性良好。因此，与对照组相比，ChABC治疗和桥插入后更多的轴突延伸到脊髓中更长的距离，其中轴突再生到PN移植物中，但生长回到脊髓中是极其有限的。这些结果表明，第一次，脊髓损伤后的细胞外基质成分的调制，促进显着的轴突再生超出了PN桥的远端回到脊髓，再生轴突可以介导的有用功能的受影响的肢体的回报。
Chondroitinase-ABC (ChABC) was applied to a cervical level 5 (C5) dorsal quadrant aspiration cavity of the adult rat spinal cord to degrade the local accumulation of inhibitory chondroitin sulfate proteoglycans. The intent was to enhance the extension of regenerated axons from the distal end of a peripheral nerve (PN) graft back into the C5 spinal cord, having bypassed a hemisection lesion at C3. ChABC-treated rats showed (1) gradual improvement in the range of forelimb swing during locomotion, with some animals progressing to the point of raising their forelimb above the nose, (2) an enhanced ability to use the forelimb in a cylinder test, and (3) improvements in balance and weight bearing on a horizontal rope. Transection of the PN graft, which cuts through regenerated axons, greatly diminished these functional improvements. Axonal regrowth from the PN graft correlated well with the behavioral assessments. Thus, many more axons extended for much longer distances into the cord after ChABC treatment and bridge insertion compared with the control groups, in which axons regenerated into the PN graft but growth back into the spinal cord was extremely limited. These results demonstrate, for the first time, that modulation of extracellular matrix components after spinal cord injury promotes significant axonal regeneration beyond the distal end of a PN bridge back into the spinal cord and that regenerating axons can mediate the return of useful function of the affected limb.