title: Assessment of Nogo-66 receptor 1 function in vivo after spinal cord injury.
abstract: BACKGROUND
  Neuronal Nogo-66 receptor 1 (NgR1) has attracted attention as a converging point for mediating the effects of myelin-associate inhibitory ligands in the central nervous system, establishing the growth-restrictive environment, and limiting axon regeneration after traumatic injury.
  
  
  OBJECTIVE
  To investigate the factors that may be contributing to the discrepancy in the importance of NgR1, which has been undermined by several studies that have shown the lack of substantial axon regeneration after spinal cord injury (SCI) in NgR1-knockout or -knockdown animal models.
  
  
  METHODS
  We used mice carrying either a homozygous or heterozygous null mutation in the NgR1 gene and subjected them to either a moderate or severe SCI.
  
  
  RESULTS
  Locomotor function assessments revealed that the level of functional recovery is affected by the degree of injury suffered. NgR1 ablation enhanced local collateral sprouting in the mutant mice. Reactive astrocytes and chondroitin sulfate proteoglycans (CSPGs) are upregulated surrounding the injury site. Matrix metalloproteinase-9, which has been shown to degrade CSPGs, was significantly upregulated in the homozygous mutant mice compared with the heterozygous or wild-type mice. However, CSPG levels remained higher in the homozygous compared with the heterozygous mice, suggesting that CSPG-degrading activity of matrix metalloproteinase-9 may require the presence of NgR1.
  
  
  CONCLUSIONS
  Genetic ablation of NgR1 may lead to significant recovery in locomotor function after SCI. The difference in locomotor recovery we observed between the groups that suffered various degrees of injury suggests that injury severity may be a confounding factor in functional recovery after SCI.
authors.affiliation: ‡Department of Neurosurgery and ‖Center for Translational Neuromedicine, University of Rochester, Rochester, New York; §Department of Neurosurgery, Fourth Affiliated Hospital of Hebei Medical University, Hebei, China; ¶Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China; and #Department of Neurosurgery, Baylor Scott & White Health, Temple, Texas.
authors.forename: Jing
authors.initials: J
authors.lastname: Tong
authors.forename: Yi
authors.initials: Y
authors.lastname: Ren
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
authors.forename: Vassilios G
authors.initials: VG
authors.lastname: Dimopoulos
authors.forename: Henry N
authors.initials: HN
authors.lastname: Kesler
authors.forename: Weimin
authors.initials: W
authors.lastname: Liu
authors.forename: Xiaosheng
authors.initials: X
authors.lastname: He
authors.forename: Maiken
authors.initials: M
authors.lastname: Nedergaard
authors.forename: Jason H
authors.initials: JH
authors.lastname: Huang
mesh_terms: D000818:Animals; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D004195:Disease Models, Animal; D058851:GPI-Linked Proteins / Q000235:genetics; D015151:Immunoblotting; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009185:Myelin Proteins / Q000235:genetics*; D009416:Nerve Regeneration / Q000235:genetics*; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface / Q000235:genetics*; D020127:Recovery of Function / Q000235:genetics*; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; C419790:Rtn4r protein, mouse; D020780:Matrix Metalloproteinase 9