We examined the possibility that the expression of adhesion molecules is regulated differently in cultured astrocytes from stroke-prone spontaneously hypertensive rats (SHRSP/IZM) rats than in those from Wistar Kyoto rats (WKY/IZM) by tumor necrosis factor-alpha (TNF-α) or hypoxia and reoxygenation (H/R) and the inhibitory effects of apigenin. It was found that the expression of vascular cell adhesion molecule-1 (VCAM-1) by TNF-α in astrocytes isolated from SHRSP/IZM was increased compared with that in WKY/IZM. The expression of monocyte chemotactic protein-1 (MCP-1) mRNA induced by H/R in SHRSP/IZM astrocytes was increased compared with that in normal oxygen concentrations. Apigenin strongly attenuated TNF-α-induced VCAM-1 mRNA and protein expression and suppressed the adhesion of U937 cells and SHRSP/IZM astrocytes. These results suggest that the expression levels of adhesion molecules during H/R affect disease outcome and can drive SHRSP/IZM to stroke. It is suggested that apigenin regulates adhesion molecule expression in reactive astrocytes during ischemia.

No abstract

Stroke-prone spontaneously hypertensive rats (SHRSP/IZM) develop severe hypertension, and more than 95% of them die of cerebral stroke, making them widely used as models of experimental cerebral ischemia. The neurons of SHRSP/IZM are more susceptible to hypoxia and reoxygenation (H/R) than those of Wistar Kyoto (WKY/IZM) rats. In particular, cerebral ischemia strongly induces neuronal death in SHRSP/IZM. We examined the effect of high dose vitamin E on the levels of glutathione (GSH) and cell death during H/R in neurons isolated from SHRSP/IZM and WKY/IZM rats. The neurons of SHRSP/IZM were more vulnerable and lost more GSH than those of the WKY/IZM rats. High dose vitamin E induced the expression of gamma glutamylcystenyl synthase (γ-GCS) mRNA, increased GSH levels, reduced neutral sphingomyelinase (N-SMase) activity, and strongly prevented neuronal death. The level of GSH was significantly lower in SHRSP/IZM than WKY/IZM neurons following exposure to hypoxia and H/R. On the other hand, the activity of N-SMase was increased in SHRSP/IZM compared to the WKY/IZM neurons. These results suggest the decrease in GSH levels of SHRSP/IZM neurons to be associated with neuronal vulnerability and that GSH, production of which is induced by a high dose of vitamin E.

Stroke-prone spontaneously hypertensive rats (SHRSP/IZM) develop severe hypertension, and more than 95% of them die of cerebral stroke, making them widely used as models of experimental cerebral ischemia. The neurons of SHRSP/IZM are more susceptible to hypoxia and reoxygenation (H/R) than those of Wistar Kyoto (WKY/IZM) rats. In particular, cerebral ischemia strongly induces neuronal death in SHRSP/IZM. We examined the effect of high dose vitamin E on the levels of glutathione (GSH) and cell death during H/R in neurons isolated from SHRSP/IZM and WKY/IZM rats. The neurons of SHRSP/IZM were more vulnerable and lost more GSH than those of the WKY/IZM rats. High dose vitamin E induced the expression of gamma glutamylcystenyl synthase (γ-GCS) mRNA, increased GSH levels, reduced neutral sphingomyelinase (N-SMase) activity, and strongly prevented neuronal death. The level of GSH was significantly lower in SHRSP/IZM than WKY/IZM neurons following exposure to hypoxia and H/R. On the other hand, the activity of N-SMase was increased in SHRSP/IZM compared to the WKY/IZM neurons. These results suggest the decrease in GSH levels of SHRSP/IZM neurons to be associated with neuronal vulnerability and that GSH, production of which is induced by a high dose of vitamin E.