title: Expression of aquaporin-4 augments cytotoxic brain edema after traumatic brain injury during acute ethanol exposure.
abstract: We previously reported that ethanol consumption affects morbidity and mortality after traumatic brain injury (TBI) by accelerating brain edema via oxidative stress after TBI. Aquaporin-4 (AQP4), a water channel, is involved in brain edema formation. In this study, we found that acute ethanol administration increased AQP4 expression after TBI, leading to severe brain edema in rats. Rats were pretreated with ethanol (3 g/kg) or dl-buthionine-(S,R)-sulfoximine (BSO; 100 mg/kg), an oxidative stressor, before TBI. Acetazolamide, an AQP4 inhibitor, was administered to ethanol-pretreated rats 3 or 12 hours after TBI. Brain edema was increased 24 hours after TBI in both the ethanol- and BSO-pretreated groups. Ethanol pretreatment induced lipid peroxidation 24 hours after TBI. Transcription factors, NF-κB and hypoxia-inducible factor-1α, were activated 3 and 24 hours after TBI in the BSO- and ethanol-pretreated groups, respectively. In the ethanol-pretreated group, AQP4 was accumulated, particularly in astrocyte end feet, 24 hours after TBI. Acetazolamide treatment improved the survival rate to 100% and decreased brain edema and AQP4 in ethanol-pretreated rats. These findings suggest that ethanol induces up-regulation of AQP4, leading to brain edema. The accumulation of AQP4 may play an important role in the augmentation of brain edema after TBI under ethanol consumption.
authors: Department of Legal Medicine and Molecular Alcohology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Ryuichi
authors: R
authors: Katada
authors: Yoko
authors: Y
authors: Nishitani
authors: Osamu
authors: O
authors: Honmou
authors: Keisuke
authors: K
authors: Mizuo
authors: Shunichiro
authors: S
authors: Okazaki
authors: Kenji
authors: K
authors: Tateda
authors: Satoshi
authors: S
authors: Watanabe
authors: Hiroshi
authors: H
authors: Matsumoto
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D051401:Aquaporin 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001929:Brain Edema / Q000139:chemically induced* / Q000378:metabolism; D001930:Brain Injuries / Q000139:chemically induced* / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000633:toxicity*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents / Q000633:toxicity*
chemical_list: D051401:Aquaporin 4; D002257:Carbonic Anhydrase Inhibitors; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; D012997:Solvents; D000431:Ethanol; D000086:Acetazolamide