title: Tert-butylhydroquinone compromises survival in murine experimental stroke.
abstract: Tert-butylhydroquinone (tBHQ), an Nrf2 signaling pathway inducer that is widely used as a food additive in the U.S., prevents oxidative stress-induced cytotoxicity in neurons. This study assesses the effects of tBHQ on ischemic stroke outcomes in mice. We measured infarct size, neurological deficits, and brain volume after tBHQ treatments in murine permanent middle cerebral artery occlusion (pMCAO) model in vivo. Further, we evaluated the regulation of tBHQ on mitochondrial function in cerebrovascular endothelial cells in vitro, which is critical to the blood-brain barrier (BBB) permeability. Our results demonstrated that tBHQ increased post-stroke mortality and worsened stroke outcomes. Mitochondrial function was suppressed by tBHQ treatment of cerebrovascular endothelial cells, and this suppression was potentiated by co-treatment with lipopolysaccharide (LPS), the bacterial mimic. These data indicate that tBHQ-exacerbated stroke damage might due to the compromised BBB permeability in permanent stroke.
authors.affiliation: Department of Physiology and Pharmacology, Center for Basic and Translational Stroke Research, West Virginia University, 1 Medical Center Drive, Morgantown, WV 26506, United States.
authors.forename: Jiahong
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Physiology and Pharmacology, Center for Basic and Translational Stroke Research, West Virginia University, 1 Medical Center Drive, Morgantown, WV 26506, United States.
authors.forename: Heng
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Physiology and Pharmacology, Center for Basic and Translational Stroke Research, West Virginia University, 1 Medical Center Drive, Morgantown, WV 26506, United States.
authors.forename: Xuefang
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Physiology and Pharmacology, Center for Basic and Translational Stroke Research, West Virginia University, 1 Medical Center Drive, Morgantown, WV 26506, United States.. Electronic address: jwsimpkins@hsc.wvu.edu.
authors.forename: James W
authors.initials: JW
authors.lastname: Simpkins
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000473:pathology; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology; D002461:Cell Line, Transformed; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000633:toxicity*; D006873:Hydroquinones / Q000633:toxicity*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000209:etiology* / Q000401:mortality*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009422:Nervous System Diseases / Q000209:etiology; D010101:Oxygen Consumption / Q000187:drug effects; D012119:Respiration / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D006873:Hydroquinones; D008070:Lipopolysaccharides; D000255:Adenosine Triphosphate; C018855:2-tert-butylhydroquinone
keywords: Nrf2; Stroke; Tert-butylhydroquinone
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