There is increasing evidence that vascular endothelial growth factor (VEGF) has a role in the development of vascular leakage in the hypoxic brain. Our recent work showed an anti-edematous effect of ghrelin on brain hypoxia. However, the underlying mechanisms by which ghrelin exerts its anti-edematous effect are still unclear. For this purpose, we examined the effects of ghrelin on VEGF expression in the hypoxic brain. Adult male Wistar rats were divided into acute or chronic controls, acute or chronic hypoxia, and ghrelin-treated acute or chronic hypoxia groups. Systemic hypoxia was induced in rats by a hypoxic chamber (O2 10-11 %) for 2 days (acute) or 10 days (chronic). Effects of ghrelin on VEGF expression were evaluated using immunoblotting. Our data revealed that acute and chronic hypoxia increased VEGF expression in both acute and chronic hypoxia (P < 0.001). Ghrelin significantly reduced this expression in hypoxic conditions (P < 0.001). Our findings demonstrated the beneficial effects of ghrelin might be mediated, at least in part, through a decline in VEGF production.
Edited by: James Jones New Findings r 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? r 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% O 2 ) 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.
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.
Cerebral ischemia is an important factor in developing neurological damage without appropriate medical treatment. Kombucha tea(KT) is a fermented beverage that produces many compounds with antioxidant power with potential health effects. This study was performed to evaluate the effect of pre-treatment of kombucha tea on brain edema, neurobehavioral, and oxidative stress in the global brain ischemia model. Adult male Wistar rats were divided into four groups include; the sham, the ischemic, and the KT-treated-ischemic groups. KT was administrated two weeks before inducing transient global cerebral ischemia at two different dosages (one and two ml/kg/day, gavage). The global brain ischemia was induced by blocking the common carotid arteries for one hour, followed by 24 hours of reperfusion. At the end of reperfusion, neurobehavioral studies were done. Brain edema was determined by dry-wet methods. Malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) levels were measured in the serum and the brain tissue. Our results showed that pre-treatment of KT significantly reduced brain edema and MDA levels in the blood and the brain. It significantly increased the total TAC and GPx levels in the blood and the brain in ischemic rats treated with KT. The CAT activity significantly increased in the blood, but it didn’t significantly change the brain. KT of pre-treatment significantly ameliorated neurobehavioral defects in the ischemic rats. Our data demonstrated that pre-treatment of KT maybe protect the brain against ischemic-reperfusion injury through a decrease in the production of lipid peroxidation and an increase in the capacity of antioxidants defense.
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