Ghrelin ameliorates blood brain barrier disruption in the systemic hypoxia

Abstract

The blood brain barrier (BBB), which serves to protect homeostasis of the central nervous system, is formed by tight junction proteins. Several studies have indicated that systemic hypoxia leads to cerebral edema through disruption of the tight junction proteins such as occludin and zonula occludens-1 (ZO-1). According to our previous studies ghrelin attenuates cerebral edema in the hypoxic brain. However, its mechanisms are not completely understood. The present study was aimed to determine the effect of ghrelin on occludin and Zo-1 in the hypoxic brain. Adult male Wistar rats were divided into acute and chronic controls, acute or chronic hypoxia, and ghrelin- treated acute or chronic hypoxia groups. Hypoxic groups were kept in a hypoxic chamber (O2 10–11%) for two days (acute) or ten days (chronic). Effects of ghrelin on occludin and ZO-1 protein levels were assessed using western blotting. Western blot analysis revealed that ZO-1 and occludin protein expression significantly decreased in acute and chronic hypoxia. Ghrelin significantly increased ZO-1 protein expression in both acute and chronic hypoxia (P < 0.05). Ghrelin also increased occludin protein expression in chronic hypoxia (P < 0.05), but did not effectively change it in acute hypoxia. Our data showed that ghrelin injection maintains occludin and ZO-1 tight junction proteins which may improve the integrity of the BBB in hypoxic condition.

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