Ghrelin ameliorates blood-brain barrier disruption during systemic hypoxia.

Abstract

What is the central question of this study? Is an anti-oedematous effect of ghrelin associated with increased expression of tight junction proteins in the hypoxic brain? What is the main finding and its importance? We showed that injection of ghrelin during acute and chronic systemic hypoxia is associated with increased expression of tight junction proteins and protection of the blood-brain barrier. Ghrelin appears to be a new therapeutic strategy for protection of the blood-brain barrier from disruption and prevention of brain oedema in hypoxic conditions. The blood-brain barrier, which serves to protect the homeostasis of the CNS, is formed by tight junction proteins. Several studies have indicated that systemic hypoxia leads to cerebral oedema through disruption of tight junction proteins, such as occludin and zonula occludens-1 (ZO-1). According to our previous studies, ghrelin attenuates cerebral oedema in the hypoxic brain. However, the mechanism is not completely understood. The present study was designed 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 control, acute or chronic hypoxia, and ghrelin-treated acute or chronic hypoxia groups. Hypoxic groups were kept in a hypoxic chamber (10-11% O2 ) for 2 (acute) or 10 days (chronic). Effects of ghrelin on occludin and ZO-1 protein levels were assessed using Western blotting. Western blot analysis revealed that the protein expression of ZO-1 and occludin decreased significantly 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 blood-brain barrier in hypoxic conditions.