| 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 | K L Brewer, J R Bethea, R P Yezierski
(Affiliation: Department of Anatomy and Cell Biology, East Carolina University, 27858, USA.)
|
| Journal | Experimental neurology
(Exp Neurol)
Vol. 159
Issue 2
Pg. 484-93
(Oct 1999)
ISSN: 0014-4886 UNITED STATES |
| PMID | 10506519
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
|
| Copyright | Copyright 1999 Academic Press. |
| Chemical References |
- Neuroprotective Agents
- Neurotoxins
- Interleukin-10
- Quisqualic Acid
|
| Topics |
- Animals
- Death
- Female
- Humans
- Inflammation
- Injections, Spinal
- Interleukin-10
(administration & dosage, therapeutic use)
- Neurons
(drug effects, pathology, physiology)
- Neuroprotective Agents
(administration & dosage, therapeutic use)
- Neurotoxins
(toxicity)
- Periaqueductal Gray
(drug effects, pathology)
- Quisqualic Acid
(toxicity)
- Rats
- Rats, Sprague-Dawley
- Spinal Cord
(drug effects, pathology)
- Spinal Cord Injuries
(chemically induced, physiopathology, prevention & control)
|
