title: Local injection of lentivirus encoding LINGO-1-shRNA promotes functional recovery in rats with complete spinal cord transection.
abstract: METHODS
  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.
  
  
  BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.affiliation: *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.
authors.forename: Jingsheng
authors.initials: J
authors.lastname: Cen
authors.forename: Hongfu
authors.initials: H
authors.lastname: Wu
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.forename: Xianyue
authors.initials: X
authors.lastname: Ren
authors.forename: Hongwu
authors.initials: H
authors.lastname: Zhang
authors.forename: Jingnan
authors.initials: J
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Wan
authors.forename: Yubin
authors.initials: Y
authors.lastname: Deng
mesh_terms: D000818:Animals; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D007278:Injections, Spinal; D016086:Lentivirus / Q000235:genetics; D008565:Membrane Proteins / Q000008:administration & dosage* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000008:administration & dosage* / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000235:genetics / Q000473:pathology / Q000628:therapy*
chemical_list: C525164:LINGO1 protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering