Neuroprotective effects of interleukin-10 following excitotoxic spinal cord injury

Kori L. Brewer, John R. Bethea, Robert P. Yezierski

Research output: Contribution to journalArticle

125 Citations (Scopus)

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 μg, 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.

Original languageEnglish
Pages (from-to)484-493
Number of pages10
JournalExperimental Neurology
Volume159
Issue number2
DOIs
StatePublished - Oct 1 1999

Fingerprint

Neuroprotective Agents
Spinal Cord Injuries
Interleukin-10
Quisqualic Acid
Wounds and Injuries
Spinal Injections
Inflammation
Animal Disease Models
Sprague Dawley Rats
Anti-Inflammatory Agents
Cytokines
Injections
Survival

Keywords

  • Cytokines
  • Inflammation
  • Neuroprotection
  • Quisqualate
  • Secondary injury

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Neuroprotective effects of interleukin-10 following excitotoxic spinal cord injury. / Brewer, Kori L.; Bethea, John R.; Yezierski, Robert P.

In: Experimental Neurology, Vol. 159, No. 2, 01.10.1999, p. 484-493.

Research output: Contribution to journalArticle

Brewer, Kori L. ; Bethea, John R. ; Yezierski, Robert P. / Neuroprotective effects of interleukin-10 following excitotoxic spinal cord injury. In: Experimental Neurology. 1999 ; Vol. 159, No. 2. pp. 484-493.
@article{839b8f055e8c48e1adacc29703d8b553,
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 μg, 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.",
keywords = "Cytokines, Inflammation, Neuroprotection, Quisqualate, Secondary injury",
author = "Brewer, {Kori L.} and Bethea, {John R.} and Yezierski, {Robert P.}",
year = "1999",
month = "10",
day = "1",
doi = "10.1006/exnr.1999.7173",
language = "English",
volume = "159",
pages = "484--493",
journal = "Experimental Neurology",
issn = "0014-4886",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Neuroprotective effects of interleukin-10 following excitotoxic spinal cord injury

AU - Brewer, Kori L.

AU - Bethea, John R.

AU - Yezierski, Robert P.

PY - 1999/10/1

Y1 - 1999/10/1

N2 - 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 μg, 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.

AB - 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 μg, 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.

KW - Cytokines

KW - Inflammation

KW - Neuroprotection

KW - Quisqualate

KW - Secondary injury

UR - http://www.scopus.com/inward/record.url?scp=0032865257&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032865257&partnerID=8YFLogxK

U2 - 10.1006/exnr.1999.7173

DO - 10.1006/exnr.1999.7173

M3 - Article

VL - 159

SP - 484

EP - 493

JO - Experimental Neurology

JF - Experimental Neurology

SN - 0014-4886

IS - 2

ER -