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

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 (80 μg/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.

► Systemic normobaric hypoxia increased brain water content in both acute and chronic hypoxia. ► Administration of ghrelin reduced brain water content only in acute hypoxia. ► Serum TNF-α levels increased in acute hypoxia and ghrelin could reduce it. ► Both acute and chronic systemic hypoxia decreased body weights. ► Administration of ghrelin prevented further weight loss in chronic hypoxia group.