The absence of the CD163 receptor has distinct temporal influences on intracerebral hemorrhage outcomes

Jenna L Leclerc, Andrew S Lampert, Claudia Loyola Amador, Brandon Schlakman, Terrie Vasilopoulos, Pia Svendsen, Søren K Moestrup, Sylvain Doré

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


    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.

    TidsskriftJournal of Cerebral Blood Flow and Metabolism
    Udgave nummer2
    Sider (fra-til)262-273
    StatusUdgivet - 2018


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