| Changes in Gene Expression during Brain Ischemia and the Effect of Pretreatment of BN52021 (PAF Antagonist). |
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Sang Ook Nam, Su Young Kim, Jin Sup Jung |
1Department of Pediatrics, College of Medicine, Pusan National University, Pusan, Korea.
2Department of Physiology, College of Medicine, Pusan National University, Pusan, Korea. |
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| Abstract |
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BACKGROUND: This study was undertaken to determine temporal changes in expression of various genes and the effect of platelet-activating factor antagonist on their expression. SUBJECTS AND METHODS: The changes in expression of various genes including interleukin-1, iNOS, TNF-alpha, ICAM-1, cPLA2, GLUT1, BDNF and Bcl-X according to time were examined using reverse-transcription polymerase chain reaction(RT-PCR) by checking at various time points after induction of middle cerebral artery(MCA) occlusion in the thrombotic and embolic models of stroke of Sprague-Dawley rats. We also examined the effect of pretreatment of a PAF antagonist, BN52021 on the expression of the same genes by RT-PCR and by in situ hybridization technique. RESULTS: The expressions of BDNF, IL-1, GLUT1, iNOS, cPLA2 and TNF-alpha were increased in ischemic brain tissue. However, the temporal profiles of their expression were variable; the peak expression was observed after 1 hour reperfusion in TNF-alpha, after 4 hours in IL-1, cPLA2 and BDNF and after 24 hours in GLUT1 and iNOS. Pretreatment of a PAF antagonist, BN52021, significantly inhibited the ischemia-induced expression of TNF-alpha, cPLA2 and iNOS without affecting the expression of the BDNF and GLUT1. In situ hybridization showed that cPLA2 expression induced by transient forebrain ischemia in dentate gyrus was ameliorated by the pretreatment of BN52021. CONCLUSION: This result indicates that BN52021, PAF antagonist, specifically inhibits expression of certain genes, which may be related to its protective effect on ischemic brain injury. |
| Key Words:
Brain ischemia, Gene expression, PAF antagonist |
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