362 CHRONOLOGICAL CHANGES OF PLASMA OXIDATIVE STRESS MARKERS IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RAT --- IN RELATION TO INCIDENCE OF CEREBROVASCULAR LESION

Abstract

Objectives: In this study, we investigated the correlation between the hypertensive cerebral injury and oxidative stress using stroke-prone spontaneously hypertensive rats (SHRSP). Methods: Male SHRSPs and normotensive Wistar-Kyoto rats (WKY) were used at every two weeks from 10 to 18 weeks of age (n=6). Plasma d-ROM, serum 8-OHdG levels as blood oxidative stress, BAP test as antioxidant capacity and the d-ROM tissue, LIPO tissue and TBARS levels in cerebral cortex as the marker of tissue oxidation and lipid peroxidation were investigated. Furthermore, we investigated the expression of GLUT-1 and Aquaporin 4 as marker of blood brain barrier and ICAM-1 (adhesion molecule in endothelial cells) by realtime PCR. Results: Plasma d-ROM level gradually increased with age in both strains. After 16 weeks of age, it remarkably increased in SHRSP. Serum 8-OHdG level also tended to be higher in SHRSP than WKY. Brain d-ROM level increased rapidly in SHRSP after 16 weeks of age. At 18 weeks of age, all of SHRSP suffered from cerebral lesion. Upregulation of GLUT-1, Aquaporin 4 and ICAM-1 genes were detected in the cerebral cortex of these SHRSPs. No differences were found in BAP, brain LIPO tissue and TBARS level between SHRSP and WKY. Conclusions: These results indicate that oxidative stress plays an important role in the pathogenesis of cerebral injuries in SHRSP. Since the elevation of blood oxidative stress markers was found prior to the onset of stroke lesions, continuous traces of oxidative stress markers could be useful as predictors of stroke in SHRSP.