Abstract:
Unsuccessful axonal regeneration in transected spinal cord injury (SCI) is mainly attributed to shortage of growth factors, inhibitory glial scar, and low intrinsic regenerating capacity of severely injured neurons. Previously, we constructed an axonal growth permissive pathway in a thoracic hemisected injury by transplantation of Schwann cells overexpressing glial-cell-derived neurotrophic factor (SCs-GDNF) into the lesion gap as well as the caudal cord and proved that this novel permissive bridge promoted the regeneration of descending propriospinal tract (dPST) axons across and beyond the lesion. In the current study, we subjected rats to complete thoracic (T11) spinal cord transections and examined whether these combinatorial treatments can support dPST axons\' regeneration beyond the transected injury. The results indicated that GDNF significantly improved graft-host interface by promoting integration between SCs and astrocytes, especially the migration of reactive astrocyte into SCs-GDNF territory. The glial response in the caudal graft area has been significantly attenuated. The astrocytes inside the grafted area were morphologically characterized by elongated and slim process and bipolar orientation accompanied by dramatically reduced expression of glial fibrillary acidic protein. Tremendous dPST axons have been found to regenerate across the lesion and back to the caudal spinal cord which were otherwise difficult to see in control groups. The caudal synaptic connections were formed, and regenerated axons were remyelinated. The hindlimb locomotor function has been improved.
摘要:
横断性脊髓损伤(SCI)轴突再生不成功主要归因于生长因子的缺乏,抑制性胶质瘢痕,严重损伤神经元的内在再生能力低。以前,我们通过将过表达胶质细胞源性神经营养因子(SCs-GDNF)的雪旺氏细胞移植到病变间隙和尾索,构建了胸半球损伤的轴突生长允许途径,并证明了这种新型允许桥促进了横过和横过病变的下行脊髓原束(dPST)轴突的再生.在目前的研究中,我们对大鼠进行了完整的胸段(T11)脊髓横断,并检查了这些组合治疗是否可以支持dPST轴突再生超过横断损伤.结果表明GDNF通过促进SCs与星形胶质细胞的整合而显著改善移植物-宿主界面,特别是反应性星形胶质细胞向SCs-GDNF区的迁移。尾部移植物区域的神经胶质反应已明显减弱。移植区域内的星形胶质细胞在形态上具有细长和细长的过程和双极取向,并伴有胶质原纤维酸性蛋白的表达显着降低。已发现巨大的dPST轴突在病变处再生并回到尾脊髓,否则在对照组中很难看到。形成了尾部突触连接,再生的轴突被再髓鞘化。后肢运动功能得到改善。