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Neuroprotection against spinal cord ischemia-reperfusion injury induced by different ischemic postconditioning methods: roles of phosphatidylinositol 3-kinase-Akt and extracellular signal-regulated kinase

Xiaojing Jiang, Chunyu Ai, Enyi Shi, Yoshiki Nakajima, Hong Ma
Anesthesiology 2009, 111 (6): 1197-205
19934862

BACKGROUND: The authors compared the neuroprotective effects induced by two ischemic postconditioning methods and sought to determine the roles of phosphatidylinositol 3-kinase-Akt and extracellular signal-regulated kinase (ERK) in this neuroprotection.

METHODS: Spinal cord ischemia was induced in rabbits by occlusion of the infrarenal aorta with a balloon catheter for 25 min. Postconditioning was accomplished by either five cycles of 1-min occlusion and 1-min reperfusion (standard postconditioning) or control of the perfusion pressure between 45 and 55 mmHg at the first 10 min of reperfusion (modified postconditioning). Motor function was assessed with the Tarlov score during a 28-day observation period. Histologic examination of lumbar spinal cords was performed. Expressions of Akt and ERK in the spinal cord were evaluated by Western blot.

RESULTS: Compared with the controls, the two postconditioning methods markedly increased Tarlov scores 1, 3, 7, and 28 days after spinal cord ischemia and number of intact motor neurons in the lumbar spinal cord. No significant difference in Tarlov scores and number of intact motor neurons was detected between the two postconditioning method groups. The two postconditioning methods enhanced the expressions of phospho-Akt and phospho-ERK in spinal cords. The neuroprotective effects and the increases in phospho-Akt and phospho-ERK were abolished by administration of phosphatidylinositol 3-kinase-Akt inhibitor LY-294002 or ERK inhibitor PD-98059.

CONCLUSIONS: The two postconditioning methods possess comparable neuroprotective effects on the spinal cord and share a common molecular mechanism, in which phosphatidylinositol 3-kinase and ERK pathways play crucial roles.

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