title: Delayed accumulation of activated macrophages and inhibition of remyelination after spinal cord injury in an adult rodent model.
abstract: OBJECTIVE
  Inhibition of remyelination is part of the complex problem of persistent dysfunction after spinal cord injury (SCI), and residual myelin debris may be a factor that inhibits remyelination. Phagocytosis by microglial cells and by macrophages that migrate from blood vessels plays a major role in the clearance of myelin debris. The object of this study was to investigate the mechanisms underlying the failure of significant remyelination after SCI.
  
  
  METHODS
  The authors investigated macrophage recruitment and related factors in rats by comparing a contusion model (representing contusive SCI with residual myelin debris and failure of remyelination) with a model consisting of chemical demyelination by lysophosphatidylcholine (representing multiple sclerosis with early clearance of myelin debris and remyelination). The origin of infiltrating macrophages was investigated using mice transplanted with bone marrow cells from green fluorescent protein-transfected mice. The changes in levels of residual myelin debris and the infiltration of activated macrophages in demyelinated lesions were investigated by immunostaining at 2, 4, and 7 days postinjury. To investigate various factors that might be involved, the authors also investigated gene expression of macrophage chemotactic factors and adhesion factors.
  
  
  RESULTS
  Activated macrophages coexpressing green fluorescent protein constituted the major cell population in the lesions, indicating that the macrophages in both models were mainly derived from the bone marrow, and that very few were derived from the intrinsic microglia. Immunostaining showed that in the contusion model, myelin debris persisted for a long period, and the infiltration of macrophages was significantly delayed. Among the chemotactic factors, the levels of monocyte chemoattractant protein-1 and granulocyte-macrophage colony-stimulating factor were lower in the contusion model at 2 and 4 days postinjury.
  
  
  CONCLUSIONS
  The results suggest that the delayed infiltration of activated macrophages is related to persistence of myelin debris after contusive SCI, resulting in the inhibition of remyelination.
authors.affiliation: Department of Neurosurgery, Tokai University School of Medicine, Isehara, Kanagawa, Japan. imai101@is.icc.u-tokai.ac.jp
authors.forename: Masaaki
authors.initials: M
authors.lastname: Imai
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Kaori
authors.initials: K
authors.lastname: Suyama
authors.forename: Takahiro
authors.initials: T
authors.lastname: Osada
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sakai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawada
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Matsumae
authors.forename: Joji
authors.initials: J
authors.lastname: Mochida
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D018932:Chemokine CCL2 / Q000032:analysis; D003288:Contusions / Q000503:physiopathology; D016207:Cytokines / Q000032:analysis; D003711:Demyelinating Diseases / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008262:Macrophage Activation / Q000502:physiology*; D019402:Macrophage Inflammatory Proteins / Q000032:analysis; D008264:Macrophages / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000502:physiology; D009103:Multiple Sclerosis / Q000503:physiopathology; D009186:Myelin Sheath / Q000502:physiology*; D010587:Phagocytosis / Q000502:physiology; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000032:analysis; D014945:Wound Healing / Q000502:physiology
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D016212:Transforming Growth Factor beta; D018799:Intercellular Adhesion Molecule-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor