title: Neuroprotective effects of interleukin-10 following excitotoxic spinal cord injury.
abstract: Intraspinal injection of quisqualic acid (QUIS) produces excitotoxic injury with pathological characteristics similar to those associated with ischemic and traumatic spinal cord injury (SCI). Inflammatory responses appear to be a major component of the secondary neuronal injury initiated by SCI and play a role in the pathogenesis of QUIS-induced injury. IL-10 is a potent antiinflammatory cytokine that has been shown to reduce inflammation and improve functional outcome in human and animal models of inflammatory diseases. We propose the administration of IL-10 following excitotoxic SCI will attenuate the inflammatory response, thus resulting in increased neuronal survival. Female, Sprague-Dawley rats were given intraspinal injections of QUIS followed by either intraspinal (5 ng, n = 8) or systemic injections (5 microgram n = 14) of IL-10. Survival times were varied (2-3 days) in order to produce a range of injury states and inflammatory involvement. When administered intraspinally, IL-10 significantly exacerbated the QUIS damage (P < 0.05), resulting in an 11.2% increase in lesion volume. When given systemically, IL-10 significantly decreased lesion volume by 18.1% in the more advanced injury (P < 0.05), but did not effect the more acute injury. These divergent effects were attributed to the modest inflammatory response in the short-term injury compared to the more robust inflammatory response in the more chronic injury. In conclusion, reducing the inflammatory response to SCI by systemic administration of IL-10 resulted in a significant reduction in neuronal damage, suggesting that targeting injury-induced inflammation may be an effective treatment strategy for acute SCI.
authors.affiliation: Department of Anatomy and Cell Biology, East Carolina University, 27858, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Brewer
authors.forename: J R
authors.initials: JR
authors.lastname: Bethea
authors.forename: R P
authors.initials: RP
authors.lastname: Yezierski
mesh_terms: D000818:Animals; D003643:Death; D005260:Female; D006801:Humans; D007249:Inflammation; D007278:Injections, Spinal; D016753:Interleukin-10 / Q000008:administration & dosage / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D009498:Neurotoxins / Q000633:toxicity*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000473:pathology; D016318:Quisqualic Acid / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D018696:Neuroprotective Agents; D009498:Neurotoxins; D016753:Interleukin-10; D016318:Quisqualic Acid