title: A novel brain injury mechanism after intracerebral hemorrhage: the interaction between heme products and the immune system.
abstract: In this paper we hypothesize a novel mechanism by which brain injury occurs after intracerebral hemorrhage. We propose the following mechanism: (1) heme that is derived from extravasated erythrocytes is degraded into bilirubin and bilirubin oxidation products (BOXes). (2) Bilirubin and BOXes activate microglia and astrocytes, which are cells with immune functions in the brain. This activation leads to release of cytokines and activation of leukocyte adhesion molecules on the luminal surface of cerebral endothelial cells. (3) Leukocytes then traffic into the brain. (4) Leukocytes, activated glial cells and cytokines contribute to injury processes. We present preliminary data in support of our hypothesis that BOXes activate glia.
authors.affiliation: Neuroscience Graduate Program, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Room 7010, Cincinnati, OH 45267, United States. loftspmc@email.uc.edu
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Loftspring
authors.forename: Craig
authors.initials: C
authors.lastname: Hansen
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Clark
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism; D001921:Brain / Q000196:embryology; D001930:Brain Injuries / Q000150:complications* / Q000175:diagnosis* / Q000276:immunology; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000276:immunology; D042783:Endothelial Cells / Q000378:metabolism; D006418:Heme / Q000378:metabolism*; D006801:Humans; D007107:Immune System; D007962:Leukocytes / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D008962:Models, Theoretical; D009457:Neuroglia / Q000378:metabolism
chemical_list: D006418:Heme; D001663:Bilirubin