Abstract 16544: The Evolution of Chemokine Release Supports a Bimodal Mechanism of Spinal Cord Ischemia and Reperfusion Injury
Background: Paraplegia remains a significant complication of thoracic aortic surgery. The mechanism of the antecedent spinal cord ischemia and reperfusion injury (IR) is largely understudied. IR often involves two injuries, an initial ischemic insult and subsequent inflammatory amplification of the injury. This mechanism is consistent with the clinical phenomenon of delayed onset paraplegia. We sought to characterize the inflammatory response in the spinal cord after IR and hypothesized that this would support a bimodal mechanism of injury.
Methods: Male C57Bl/6 mice were subjected to 5 minutes of aortic arch and left subclavian occlusion to generate spinal cord ischemia and subsequently reperfused. Functional outcomes were measured and scored in 12 hour intervals. Spinal cords were harvested after 0, 6, 12, 18, 24, 36, and 48 hours of reperfusion. Cytokine levels were analyzed using a mouse magnetic bead based multiplex immunoassay. Standard histologic stains were used to assess spinal cord histology at various reperfusion times.
Results: Twenty-three cytokines were selected for analysis. Inflammatory chemokine concentrations (Il-1β, Il-6, keratinocyte derived cytokine (KC), monocyte chemotactic protein-1, RANTES, and TNFα) peaked at 6 hours and 36 to 48 hours after reperfusion. Functional scores reflected initial gain in function with subsequent decline, inversely proportional to cytokine levels. Standard hematoxylin and eosin histology supported our immunologic and functional findings.
Conclusion: Spinal cord ischemia and reperfusion injury occurs in two phases, correlating to increases in inflammatory chemokines early and late in reperfusion. This observation corresponds to the clinical phenomenon of delayed onset paraplegia. Understanding the molecular pathogenesis of this injury will allow future intervention to treat and prevent this devastating complication.
- © 2011 by American Heart Association, Inc.