Ischemic postconditioning protects the spinal cord from ischemia–reperfusion injury via modulation of redox signaling

• Published in: The Journal of thoracic and cardiovascular surgery Vol. 146; no. 3; pp. 688 - 695
• Main Authors: Song, Wenying, MD, Sun, Jing, MD, PhD, Su, Binxiao, MD, PhD, Yang, Rui, MD, Dong, Hailong, MD, PhD, Xiong, Lize, MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 01.09.2013
• Subjects: Animals; Antioxidants - metabolism; Cardiothoracic Surgery; Catalase - genetics; Catalase - metabolism; Disease Models, Animal; Drug Administration Schedule; Free Radical Scavengers - administration & dosage; Gene Expression Regulation, Enzymologic; Ischemic Postconditioning; Male; Oxidation-Reduction; Oxidative Stress - drug effects; Paraplegia - metabolism; Paraplegia - pathology; Paraplegia - prevention & control; Rabbits; Reactive Oxygen Species - metabolism; Reperfusion Injury - genetics; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Spinal Cord - blood supply; Spinal Cord - drug effects; Spinal Cord - metabolism; Spinal Cord - pathology; Spinal Cord Ischemia - genetics; Spinal Cord Ischemia - metabolism; Spinal Cord Ischemia - pathology; Spinal Cord Ischemia - therapy; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; Time Factors; NSE; postconditioning; neuron-specific enolase; N-2-mercaptopropionylglycine; MPG; 38; ischemic preconditioning; SOD; I/R; 38.1; 38.2; ischemia–reperfusion; superoxide dismutase; ROS; reactive oxygen species; PostC; GAPDH; IPC; glyceraldehyde 3-phosphate dehydrogenase
• ISSN: 0022-5223; 1097-685X
• DOI: 10.1016/j.jtcvs.2012.11.039

Background It is well known that ischemic postconditioning reduces ischemic–reperfusion injury, but the underlying mechanism is not fully understood. The current study investigated the role of reactive oxygen species–mediated upregulation of endogenous antioxidant enzymes in the generation of a protective effect induced by ischemic postconditioning against spinal cord reperfusion injury in the rabbit. Methods New Zealand White rabbits were randomly allocated to sham, ischemia–reperfusion, and postconditioning groups (3 cycles of 30 seconds of reperfusion and 30 seconds of occlusion during the onset of reperfusion). Spinal cord ischemia was induced by clamping the infrarenal abdominal aorta for 20 minutes in the ischemia–reperfusion and postconditioning groups. Forty-eight hours after reperfusion, the neurologic status of the lower limbs was assessed. Blood samples were collected for analysis of serum neuron-specific enolase levels, and the lumbar spinal cord segments (L5-7) were harvested for histopathologic and antioxidant enzyme activities and mRNA analysis with or without administration of N-2-mercaptopropionylglycine (an effective oxygen free radical scavenger) given at different reperfusion times. Results Continuous administration of N-2-mercaptopropionylglycine for 13 minutes, starting at 10 minutes before (but not 10 minutes after) the beginning of reperfusion, attenuated the neuroprotective effect of postconditioning against spinal cord ischemia and reversed the increase in activity of the antioxidant enzymes superoxide dismutase and catalase in spinal cord tissue subjected to ischemic postconditioning. Conclusions The results indicate that reactive oxygen species–triggered upregulation of endogenous antioxidant enzyme activities may be involved in the mechanism of neuroprotection of ischemic postconditioning.