title: 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 (O(2) 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.
authors.affiliation: Neuroscience Research Center of Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Fezzeh
authors.initials: F
authors.lastname: Hossienzadeh
authors.forename: Shirin
authors.initials: S
authors.lastname: Babri
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Alipour
authors.forename: Hadi
authors.initials: H
authors.lastname: Ebrahimi
authors.forename: Gisou
authors.initials: G
authors.lastname: Mohaddes
mesh_terms: D000208:Acute Disease; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001929:Brain Edema / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D002908:Chronic Disease; D054439:Ghrelin / Q000494:pharmacology* / Q000627:therapeutic use; D000860:Hypoxia / Q000150:complications*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054439:Ghrelin; D014409:Tumor Necrosis Factor-alpha