title: An in vitro model of aneurysmal subarachnoid hemorrhage: oxidation of unconjugated bilirubin by cytochrome oxidase.
abstract: Aneurysmal subarachnoid hemorrhage is a stroke subtype with high rates of mortality and morbidity. Cerebral vasospasm can lead to ischemic injury or death and is a common complication of aneurysmal subarachnoid hemorrhage, usually occurring 3-9 days afterwards. The cause of vasospasm is not known. Recently, there has been strong evidence that vasoactive oxidation products of bilirubin may be involved. Currently, the factors that lead to bilirubin oxidation are poorly characterized. In this study, we have designed an in vitro model of hemorrhagic stroke in order to investigate conditions that promote the oxidation of bilirubin to form vasoactive compounds. Using our model, we created a basic hematoma system of blood, CSF, and hemeoxygenase-1. We manipulated this system in various ways, incubated it and determined the concentration of vasoactive bilirubin oxidation products that resulted. Conditions where cytochrome oxidase was stimulated caused an increase bilirubin oxidation products (292.6 +/- 39.9 micromol/L respectively, vs. 79.3 +/- 1.3 micromol/L for the basic reaction, p < 0.05), which was attenuated by cyanide. Our data suggest that bilirubin oxidation products may be produced by oxidation(s) requiring an oxygen-utilizing enzyme like cytochrome oxidase.
authors.affiliation: Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USAThe Neuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Loftspring
authors.affiliation: Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USAThe Neuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: William L
authors.initials: WL
authors.lastname: Wurster
authors.affiliation: Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USAThe Neuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: Gail J
authors.initials: GJ
authors.lastname: Pyne-Geithman
authors.affiliation: Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USAThe Neuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Clark
mesh_terms: D000818:Animals; D001099:Arachnoid / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism*; D001769:Blood / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000378:metabolism; D003486:Cyanides / Q000494:pharmacology; D003576:Electron Transport Complex IV / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006801:Humans; D008297:Male; D008954:Models, Biological; D009924:Organ Culture Techniques; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D013346:Subarachnoid Space / Q000378:metabolism / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D003486:Cyanides; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D003576:Electron Transport Complex IV; D001663:Bilirubin