Jingsheng Cen1, Hongfu Wu, Jue Wang, Xianyue Ren, Hongwu Zhang, Jingnan Wang, Yong Wan, Yubin Deng. 1. *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.
Abstract
STUDY DESIGN: 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). OBJECTIVE: To demonstrate the neuroregenerative and neuroprotective effects of LINGO-1 RNAi on complete transection SCI rats. SUMMARY OF BACKGROUND DATA: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
STUDY DESIGN: 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). OBJECTIVE: To demonstrate the neuroregenerative and neuroprotective effects of LINGO-1 RNAi on complete transection SCI rats. SUMMARY OF BACKGROUND DATA: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Karl J M Hanf; Joseph W Arndt; YuTing Liu; Bang Jian Gong; Mia Rushe; Richelle Sopko; Ramiro Massol; Benjamin Smith; Yan Gao; Isin Dalkilic-Liddle; Xinhua Lee; Shanell Mojta; Zhaohui Shao; Sha Mi; R Blake Pepinsky Journal: MAbs Date: 2020 Jan-Dec Impact factor: 5.857