title: The absence of the CD163 receptor has distinct temporal influences on intracerebral hemorrhage outcomes.
abstract: Hemoglobin (Hb) toxicity precipitates secondary brain damage following intracerebral hemorrhage (ICH). CD163 is an anti-inflammatory Hb scavenger receptor and CD163-positive macrophages/microglia locally accumulate post-bleed, yet no studies have investigated the role of CD163 after ICH. ICH was induced in wildtype and CD163-/-mice and various anatomical and functional outcomes were assessed. At 3 d, CD163-/-mice have 43.4 ± 5.0% (p = 0.0002) and 34.8 ± 3.4% (p = 0.0003) less hematoma volume and tissue injury, respectively. Whereas, at 10 d, CD163-/-mice have 49.2 ± 15.0% larger lesions (p = 0.0385). An inflection point was identified, where CD163-/-mice perform better on neurobehavioral testing and have less mortality before 4 d, but increased mortality and worse function after 4 d (p = 0.0389). At 3 d, CD163-/-mice have less Hb, iron, and blood-brain barrier dysfunction, increased astrogliosis and neovascularization, and no change in heme oxygenase 1 (HO1) expression. At 10 d, CD163-/-mice have increased iron and VEGF immunoreactivity, but no significant change in HO1 or astrogliosis. These novel findings reveal that CD163 deficiency has distinct temporal influences following ICH, with early beneficial properties but delayed injurious effects. While it is unclear why CD163 deficiency is initially beneficial, the late injurious effects are consistent with the key anti-inflammatory role of CD163 in the recovery phase of tissue damage.
authors.affiliation: 1 Department of Anesthesiology, University of Florida, USA.|2 Department of Neuroscience, University of Florida, USA.
authors.forename: Jenna L
authors.initials: JL
authors.lastname: Leclerc
authors.affiliation: 1 Department of Anesthesiology, University of Florida, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Lampert
authors.affiliation: 1 Department of Anesthesiology, University of Florida, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Loyola Amador
authors.affiliation: 1 Department of Anesthesiology, University of Florida, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Schlakman
authors.affiliation: 1 Department of Anesthesiology, University of Florida, USA.
authors.forename: Terrie
authors.initials: T
authors.lastname: Vasilopoulos
authors.affiliation: 3 Institute of Molecular Medicine, University of Southern Denmark, Denmark.
authors.forename: Pia
authors.initials: P
authors.lastname: Svendsen
authors.affiliation: 3 Institute of Molecular Medicine, University of Southern Denmark, Denmark.|4 Department of Biomedicine, Aarhus University, Denmark.|5 Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Denmark.
authors.forename: Søren K
authors.initials: SK
authors.lastname: Moestrup
authors.affiliation: 1 Department of Anesthesiology, University of Florida, USA.|2 Department of Neuroscience, University of Florida, USA.|6 Departments of Neurology, Psychology, Psychiatry, and Pharmaceutics, University of Florida, USA.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Doré
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics* / Q000378:metabolism; D001812:Blood-Brain Barrier; D001921:Brain / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D005911:Gliosis / Q000209:etiology / Q000235:genetics; D006406:Hematoma / Q000235:genetics / Q000473:pathology; D006454:Hemoglobins / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000235:genetics; D011597:Psychomotor Performance; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D020127:Recovery of Function; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D006454:Hemoglobins; D011956:Receptors, Cell Surface; D007501:Iron
keywords: Gliosis; heme oxygenase; iron; oxidative stress; stroke