Effect of ghrelin on brain edema induced by acute and chronic systemic hypoxia

Abstract: Hypoxia is an important pathogenic factor for the induction of vascular leakage and brain edema formation. Recent studies suggest a role for TNF-α in the induction of brain edema. Ghrelin attenuates the synthesis of TNF-α following subarachnoid hemorrhage and traumatic brain injury (TBI). Therefore, we examined the effects of ghrelin on the brain edema, serum TNF-α levels and body weight in a systemic hypoxia model. Adult male Wistar rats were divided into acute and chronic controls, acute or chronic hypoxia and ghrelin-treated (80μg/kg/ip/daily) acute or chronic hypoxia groups. Systemic hypoxia was induced in rats by a normobaric hypoxic chamber (O2 11%) for two days (acute) or ten days (chronic). Effect of ghrelin on brain edema and serum TNF-α levels was assessed by dry–wet and ELISA method, respectively. The results showed that acute (P <0.001) and chronic (P <0.05) hypoxia caused an increase of brain water content. Administration of ghrelin only in the acute hypoxia group significantly (P <0.001) reduced brain water content. Acute hypoxia caused an increase of serum TNF-α level (P <0.001) and ghrelin significantly (P <0.001) reduced it. TNF-α level in chronic hypoxia did not change significantly. Both acute and chronic hypoxia decreased body weight significantly (P <0.001) and administration of ghrelin only could prevent further weight loss in chronic hypoxia group (P <0.001). Our findings show that administration of ghrelin may be useful in reducing brain edema induced by acute systemic hypoxia and at least part of the anti-edematous effects of ghrelin is due to decrease of serum TNF-α levels. [Copyright &y& Elsevier]