title: Immunoglobulin G (IgG) attenuates neuroinflammation and improves neurobehavioral recovery after cervical spinal cord injury.
abstract: BACKGROUND
  Evidence suggests that the inflammatory events in the acute phase of spinal cord injury (SCI) exacerbate the initial trauma to the cord leading to poor functional recovery. As a result, minimizing the detrimental aspects of the inflammatory response after SCI is a promising treatment strategy. In this regard, immunoglobulin G (IgG) from pooled human serum is a promising treatment candidate. Due to its putative, though poorly characterized immuno-modulatory effects, IgG has been used clinically to treat neuroinflammatory disorders such as Guillain-Barré syndrome, but its effects in neurotrauma remain largely unexplored.
  
  
  METHODS
  This study examines the potential neuroprotective effects of IgG in a well-characterized cervical model of SCI. Female Wistar rats were subject to moderate-severe clip compression injury at the C7-T1 level. IgG (0.4 g/kg) or saline was injected intravenously to randomly selected animals at 15 min post SCI. At several time points post SCI, biochemical assays, histology and immunohistochemistry analyses, and neurobehavioral assessments were used to examine the neuroprotective effects of IgG at the molecular, cellular, and neurobehavioral levels.
  
  
  RESULTS
  We found that intravenous treatment of IgG following acute clip-compression SCI at C7-T1 significantly reduced two important inflammatory cytokines: interleukin (IL)-1β and IL-6. This early reduction in pro-inflammatory signaling was associated with significant reductions in neutrophils in the spinal cord and reductions in the expression of myeloperoxidase and matrix metalloproteinase-9 in the injured spinal cord at 24 h after SCI. These beneficial effects of IgG were associated with enhanced tissue preservation, improved neurobehavioral recovery as measured by the BBB and inclined plane tests, and enhanced electrophysiological evidence of central axonal conduction as determined by motor-evoked potentials.
  
  
  CONCLUSIONS
  The findings from this study indicate that IgG is a novel immuno-modulatory therapy which shows promise as a potential treatment for SCI.
authors.affiliation: Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Dung Hoang
authors.initials: DH
authors.lastname: Nguyen
authors.forename: Newton
authors.initials: N
authors.lastname: Cho
authors.forename: Kajana
authors.initials: K
authors.lastname: Satkunendrarajah
authors.forename: James W
authors.initials: JW
authors.lastname: Austin
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Michael G
authors.initials: MG
authors.lastname: Fehlings
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002921:Cicatrix / Q000188:drug therapy / Q000209:etiology; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D004660:Encephalitis / Q000188:drug therapy* / Q000209:etiology; D004797:Enzyme-Linked Immunosorbent Assay; D019054:Evoked Potentials, Motor / Q000187:drug effects; D005121:Extremities / Q000503:physiopathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020556:Neutrophil Infiltration / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy; D014018:Tissue Distribution
chemical_list: C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G; D053583:Interleukin-1beta; D015850:Interleukin-6; D008840:Microfilament Proteins; D018696:Neuroprotective Agents; D009195:Peroxidase; D020780:Matrix Metalloproteinase 9