Cen Jingsheng, Wu Hongfu, Wang Jue, Ren Xianyue, Zhang Hongwu, Wang Jingnan, Wan Yong, Deng Yubin
*Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China †Department of Physiology, Guangdong Medical College, Dongguan, China; and ‡Research Center of Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Spine (Phila Pa 1976). 2013 Sep 1;38(19):1632-9. doi: 10.1097/BRS.0b013e31829dd58f.
We used a complete spinal cord transection model and locomotor function, histological, and immunohistochemical examinations to evaluate the effects of local injection of lentivirus/LINGO-1-short hairpin RNA (VL) on rats with spinal cord injury (SCI).
To demonstrate the neuroregenerative and neuroprotective effects of LINGO-1 RNAi on complete transection SCI rats.
LINGO-1 has been reported as a negative regulator of axonal sprouting and its antagonist was determined to improve functional outcomes in SCI rats. However, it has not been assessed whether blockade of LINGO-1 mediated by lentivirus vectors could stimulate neural recovery after SCI.
Complete spinal cord transection was made at T10 level. Suspension of lentivirus vectors encoding LINGO-1-short hairpin RNA was injected into the lesion gap. Controls received control vectors in the same manner and the sham group was subjected to laminectomy only. The Basso-Beattie-Bresnahan scale and surface righting reflex test were used to evaluate functional outcomes. Finally, the spinal cords were harvested for histological and immunohistochemical analysis.
The treatment with VL improved Basso-Beattie-Bresnahan scores and surface righting reflex after SCI. Tissue repair was facilitated and the cavity area was significantly decreased in VL-treated animals. More sprouting and myelinated nerve fibers were detected within the injured site in the VL group as compared with the control. In addition, the number of survival neurons and oligodendrocytes around the epicenter was notably higher under the VL condition.
Local injection of lentivirus/LINGO-1-short hairpin RNA after complete transection of spinal cord resulted in meaningful histological and functional outcomes in rats. The mechanism of VL protection may be related to its promotion of axonal sprouting, remyelination, and cell survival.
我们使用完全性脊髓横断模型以及运动功能、组织学和免疫组化检查，来评估局部注射慢病毒/LINGO-1短发夹RNA（VL）对脊髓损伤（SCI）大鼠的影响。
证明LINGO-1 RNA干扰对完全性横断SCI大鼠的神经再生和神经保护作用。
LINGO-1已被报道为轴突发芽的负调节因子，其拮抗剂被确定可改善SCI大鼠的功能结局。然而，尚未评估慢病毒载体介导的LINGO-1阻断是否能刺激SCI后的神经恢复。
在T10水平进行完全性脊髓横断。将编码LINGO-1短发夹RNA的慢病毒载体悬浮液注入损伤间隙。对照组以相同方式接受对照载体，假手术组仅行椎板切除术。使用Basso-Beattie-Bresnahan评分和表面翻正反射试验评估功能结局。最后，取脊髓进行组织学和免疫组化分析。
VL治疗改善了SCI后的Basso-Beattie-Bresnahan评分和表面翻正反射。VL治疗的动物促进了组织修复，空洞面积显著减小。与对照组相比，VL组在损伤部位检测到更多的发芽和有髓神经纤维。此外，在VL条件下，震中周围存活神经元和少突胶质细胞的数量明显更多。
脊髓完全横断后局部注射慢病毒/LINGO-1短发夹RNA在大鼠中产生了有意义的组织学和功能结局。VL保护的机制可能与其促进轴突发芽、髓鞘再生和细胞存活有关。
