Chondroitinase ABC enhances axonal regrowth through Schwann cell-seeded guidance channels after spinal cord injury
Chondroitinase ABC enhances axonal regrowth through Schwann cell-seeded guidance channels after spinal cord injury
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DOI：
10.1096/fj.03-0196fje
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发表时间：
2004-01-01
期刊：
影响因子：
4.8
通讯作者：
Xu, XM
中科院分区：
文献类型：
--
作者：
Chau, CH;Shum, DKY;Xu, XM
将雪旺细胞接种通道移植到半切的成年大鼠胸脊髓中，作为桥接受损脊髓的策略已经过测试。尽管成功引导轴突生长进入移植物，但穿过远端移植物-宿主界面进入宿主脊髓的再生受到限制。我们假设沉积在界面神经胶质前部的硫酸软骨素（CS）糖型构成了轴突生长到宿主索中的分子屏障。由于体外纯化的星形胶质细胞沉积的 CS 糖型可通过软骨素酶 ABC 消化去除，因此我们尝试通过将酶输注到界面的宿主侧来实现同样的目的。到治疗后一个月，大量的再生轴突穿过巨噬细胞/小胶质细胞反应减弱的界面，并且 CS 免疫阳性率降低。轴突延伸至尾索达 5 毫米，而注射载体的对照组则为零。再生组织索中轴突-雪旺细胞单位的束状组织在酶处理的索中比在载体注入的对照中保存得更好。我们得出的结论是，在神经胶质增生期间沉积在远端移植物-宿主界面的CS糖型可以通过软骨素酶ABC的体内作用来清除，从而改善轴突再生到宿主脊髓中的前景。
Grafting of Schwann cell-seeded channels into hemisected adult rat thoracic spinal cords has been tested as a strategy to bridge the injured cord. Despite success in guiding axonal growth into the graft, regeneration across the distal graft-host interface into the host spinal cord was limited. We hypothesized that chondroitin sulfate (CS) glycoforms deposited at the gliotic front of the interface constitute a molecular barrier to axonal growth into the host cord. Because CS glycoforms deposited by purified astrocytes in vitro were removable by digestion with chondroitinase ABC, we attempted to achieve likewise by infusion of the enzyme to the host side of the interface. By I month post-treatment, significant numbers of regenerating axons crossed an interface that was subdued in macrophage/microglia reaction and decreased in CS-immunopositivity. The axons extended as far into the caudal cord as 5 mm, in contrast to nil in vehicle-infused controls. Fascicular organizations of axon-Schwann cell units within the regenerated tissue cable were better-preserved in enzyme-treated cords than in vehicle-infused controls. We conclude that CS glycoforms deposited during gliosis at the distal graft-host interface could be cleared by the in vivo action of chondroitinase ABC to improve prospects of axonal regeneration into the host spinal cord.