The Evolution of Chemokine Release Supports a Bimodal Mechanism of Spinal Cord Ischemia and Reperfusion Injury

[摘要] Background-Paraplegia remains a devastating complication of thoracic aortic surgery. The mechanism of the antecedent spinal cord ischemia and reperfusion injury (IR) remains poorly described. IR involves 2 injuries, an initial ischemic insult and subsequent inflammatory amplification of the injury. This mechanism is consistent with the clinical phenomenon of delayed onset paraplegia. This study sought to characterize the inflammatory response in the spinal cord after IR and hypothesized that this would support a bimodal mechanism of injury. Methods and Results-Male C57Bl/6 mice were subjected to 5 minutes of aortic arch and left subclavian occlusion with subsequent reperfusion to generate spinal cord ischemia. Functional outcomes were scored at 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. Inflammatory chemokine concentrations (interleukin [IL]-1 beta, IL-6, keratinocyte-derived cytokine, macrophage inflammatory protein-1 alpha, monocyte chemotactic protein-1, RANTES, and tumor necrosis factor-alpha) 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. Immunofluorescent staining demonstrated microglia activation at 12 and 48 hours. Conclusions-Spinal cord ischemia and reperfusion injury occurs in 2 phases, correlating to increases in inflammatory chemokines release and microglial activation. These observations chronologically parallel the too-common clinical syndrome of delayed-onset paraplegia. Understanding the molecular pathogenesis of this injury may allow future intervention to prevent this devastating complication. (Circulation. 2012;126[suppl 1]:S110-S117.)

[效力级别]  Proceedings Paper

[关键词] DISTAL AORTIC PERFUSION;ANEURYSMS;REPAIR;MODEL;RISK;PARAPLEGIA;EXPRESSION;RECOVERY