title: CD11d Antibody Treatment Improves Recovery in Spinal Cord-Injured Mice.
abstract: Acute administration of a monoclonal antibody (mAb) raised against the CD11d subunit of the leukocyte CD11d/CD18 integrin after spinal cord injury (SCI) in the rat greatly improves neurological outcomes. This has been chiefly attributed to the reduced infiltration of neutrophils into the injured spinal cord in treated rats. More recently, treating spinal cord-injured mice with a Ly-6G neutrophil-depleting antibody was demonstrated to impair neurological recovery. These disparate results could be due to different mechanisms of action utilized by the two antibodies, or due to differences in the inflammatory responses between mouse and rat that are triggered by SCI. To address whether the anti-CD11d treatment would be effective in mice, a CD11d mAb (205C) or a control mAb (1B7) was administered intravenously at 2, 24, and 48 h after an 8-g clip compression injury at the fourth thoracic spinal segment. The anti-CD11d treatment reduced neutrophil infiltration into the injured mouse spinal cord and was associated with increased white matter sparing and reductions in myeloperoxidase (MPO) activity, reactive oxygen species, lipid peroxidation, and scar formation. These improvements in the injured spinal cord microenvironment were accompanied by increased serotonin (5-HT) immunoreactivity below the level of the lesion and improved locomotor recovery. Our results with the 205C CD11d mAb treatment complement previous work using this anti-integrin treatment in a rat model of SCI.
authors: The Spinal Cord Injury Team, Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada. abrown@robarts.ca
authors: Nicole M
authors: NM
authors: Geremia
authors: Feng
authors: F
authors: Bao
authors: Trina E
authors: TE
authors: Rosenzweig
authors: Todd
authors: T
authors: Hryciw
authors: Lynne
authors: L
authors: Weaver
authors: Gregory A
authors: GA
authors: Dekaban
authors: Arthur
authors: A
authors: Brown
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001369:Axons / Q000502:physiology; D039481:CD11b Antigen / Q000276:immunology*; D003094:Collagen / Q000096:biosynthesis; D005260:Female; D007150:Immunohistochemistry; D008124:Locomotion / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000502:physiology; D020556:Neutrophil Infiltration / Q000187:drug effects; D009195:Peroxidase / Q000096:biosynthesis; D020127:Recovery of Function; D012701:Serotonin / Q000096:biosynthesis; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D039481:CD11b Antigen; D012701:Serotonin; D003094:Collagen; D009195:Peroxidase