Administration of ghrelin associated with decreased expression of matrix metalloproteinase-9 following normobaric systemic hypoxia in the brain

Abstract

Abstract Objective. According to our previous studies, ghrelin protects blood brain barrier (BBB) integrity and it attenuates hypoxia-induced brain edema in the hypoxic conditions. However, the underlying mechanisms remain poorly understood. Several studies suggest a role for matrix metal-loproteinase-9 (MMP9) in the BBB disruption and cerebral edema formation. The present study was conducted to determine the effect of ghrelin on MMP9 protein expression in the model of acute and chronic systemic hypoxia. Methods. Adult male Wistar rats were divided into acute or chronic controls, acute or chronic hypoxia and ghrelin-treated acute or chronic hypoxia groups. The hypoxic groups were kept in the hypoxic chamber (10–11% O2) for two (acute) or ten days (chronic). Effect of ghrelin on MMP9 protein expression was assessed using immunoblotting. Results. Our results showed that acute and chronic systemic hypoxia increased the MMP9 protein expression in the brain (p<0.001). Treatment with ghrelin significantly attenuated this expression in the cerebral hypoxia (p<0.05). Conclusion. Our results demonstrate that the neuroprotective effects of ghrelin may be mediated, in part, by decreasing in MMP9 production in the hypoxic brain.