Combinatory repair strategy to promote axon regeneration and functional recovery after chronic spinal cord injury.
Combinatory repair strategy to promote axon regeneration and functional recovery after chronic spinal cord injury.
复制标题
慢性脊髓损伤后促进轴突再生和功能恢复的组合修复策略。
DOI：
10.1038/s41598-017-09432-6
复制
发表时间：
2017-08-21
影响因子：
4.6
通讯作者：
Lee YS
中科院分区：
文献类型：
--
作者：
DePaul MA;Lin CY;Silver J;Lee YS
挫伤性脊髓损伤后8周，我们通过囊腔建立了周围神经移植桥（PNG），并用酸性成纤维细胞生长因子（aFGF）和软骨素酶ABC（ChABC）处理移植物/宿主界面。这种组合策略显着增强了宿主星形胶质细胞和移植施万细胞之间的整合，使其能够强劲生长，特别是儿茶酚胺能轴突，穿过移植物并返回远端脊髓。在aFGF+ChABC的情况下，较少的儿茶酚胺能轴突进入移植物，没有轴突退出，雪旺细胞和星形胶质细胞未能整合。与急性桥接修复的脊髓形成鲜明对比的是，在慢性修复的脊髓中，只有低水平的多巴胺能轴突再生到移植物中，没有证据表明重新进入脊髓。轴突再生的失败与SOCS 3表达的急剧增加密切相关。虽然再生总体上比急性期更有限，但我们在慢性损伤动物中的组合策略防止了与侵入性修复策略相关的运动行为和膀胱生理学结果的下降。这些结果表明，PNG+aFGF+ChABC治疗慢性挫伤的脊髓可以为随着时间的推移保持生长潜力的某些神经元群体的再生提供允许的底物，并导致功能改善。
Eight weeks post contusive spinal cord injury, we built a peripheral nerve graft bridge (PNG) through the cystic cavity and treated the graft/host interface with acidic fibroblast growth factor (aFGF) and chondroitinase ABC (ChABC). This combinatorial strategy remarkably enhanced integration between host astrocytes and graft Schwann cells, allowing for robust growth, especially of catecholaminergic axons, through the graft and back into the distal spinal cord. In the absence of aFGF+ChABC fewer catecholaminergic axons entered the graft, no axons exited, and Schwann cells and astrocytes failed to integrate. In sharp contrast with the acutely bridge-repaired cord, in the chronically repaired cord only low levels of serotonergic axons regenerated into the graft, with no evidence of re-entry back into the spinal cord. The failure of axons to regenerate was strongly correlated with a dramatic increase of SOCS3 expression. While regeneration was more limited overall than at acute stages, our combinatorial strategy in the chronically injured animals prevented a decline in locomotor behavior and bladder physiology outcomes associated with an invasive repair strategy. These results indicate that PNG+aFGF+ChABC treatment of the chronically contused spinal cord can provide a permissive substrate for the regeneration of certain neuronal populations that retain a growth potential over time, and lead to functional improvements.
登录
查看更多内容
DOI：
10.1523/jneurosci.2973-12.2013
发表时间：
2013-03-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Deng LX;Deng P;Ruan Y;Xu ZC;Liu NK;Wen X;Smith GM;Xu XM
通讯作者：
Xu XM
影响因子：
3.7
作者：
DePaul MA;Lin CY;Silver J;Lee YS
通讯作者：
Lee YS
DOI：
10.1152/ajpregu.00142.2006
发表时间：
2007-04-01
影响因子：
2.8
作者：
Dolber, Paul C.;Gu, Baojun;Reiter, Jerome P.
通讯作者：
Reiter, Jerome P.
影响因子：
6.6
作者：
Chen, Jiasheng;Gu, Baojun;Andersson, Karl-Erik
通讯作者：
Andersson, Karl-Erik
影响因子：
5.3
作者：
Coumans, JV;Lin, TTS;Bregman, BS
通讯作者：
Bregman, BS