Immunoglobulin G (IgG) attenuates neuroinflammation and improves neurobehavioral recovery after cervical spinal cord injury. J Neuroinflammation 2012 Sep 21;9:224
Date
09/25/2012Pubmed ID
22998664Pubmed Central ID
PMC3503837DOI
10.1186/1742-2094-9-224Scopus ID
2-s2.0-84866478622 (requires institutional sign-in at Scopus site) 57 CitationsAbstract
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.
CONCLUSION: The findings from this study indicate that IgG is a novel immuno-modulatory therapy which shows promise as a potential treatment for SCI.
Author List
Nguyen DH, Cho N, Satkunendrarajah K, Austin JW, Wang J, Fehlings MGAuthor
Kajana Satkunendrarajah PhD Associate Professor in the Neurosurgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Analysis of VarianceAnimals
Astrocytes
Behavior, Animal
Calcium-Binding Proteins
Cicatrix
Disease Models, Animal
Drug Administration Routes
Encephalitis
Enzyme-Linked Immunosorbent Assay
Evoked Potentials, Motor
Extremities
Female
Gene Expression Regulation
Glial Fibrillary Acidic Protein
Humans
Immunoglobulin G
Interleukin-1beta
Interleukin-6
Matrix Metalloproteinase 9
Microfilament Proteins
Neuroprotective Agents
Neutrophil Infiltration
Peroxidase
Psychomotor Performance
Rats
Rats, Wistar
Recovery of Function
Spinal Cord Injuries
Tissue Distribution
