Abstract 151: CD163 Has Distinct Temporal Influences on Intracerebral Hemorrhage Outcomes

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Abstract

Extracorpuscular hemoglobin (Hb)-induced toxicity following intracerebral hemorrhage (ICH) precipitates secondary brain damage and poor outcomes. CD163 is the Hb scavenger receptor with potent anti-inflammatory effects and CD163-positive macrophages/microglia accumulate in the brain with time post-ICH, 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 temporally assessed by histology and neurobehavioral testing. Acutely, CD163-/- mice have 33.2±4.5% (p<0.0001), 43.4±5.0% (p=0.0002), and 34.8±3.4% (p=0.0003) less lesion volume, hematoma volume, and tissue injury, respectively. Whereas, at 10d, CD163-/- mice have 49.2±15.0% larger lesion volumes (p=0.0385). Temporal data inspection revealed an inflection point at 4d, where CD163-/- mice perform significantly better on neurobehavioral testing and have less mortality before 4d, but increased mortality and worse function after 4d (p<0.05). Histology at 72h shows that CD163-/- mice have significantly less Hb, iron, and blood-brain barrier dysfunction, increased astrogliosis and cortical neovascularization, and no change in HO1 expression. At 10d, CD163-/- mice have increased iron and hematomal VEGF immunoreactivity, no change in HO1 expression, and decreased astrogliosis. These novel findings reveal that CD163 deficiency has distinct temporal influences on ICH outcomes, with early beneficial properties but delayed injurious effects. While it is unclear why CD163 deficiency is initially beneficial, the late injurious effects of absent CD163 are consistent with the key anti-inflammatory role of the receptor in the recovery phase of tissue damage. CD163 may represent a key targetable immunomodulatory receptor after ICH.

Funding: This work was supported by NIH grants F31NS086441 (JLL) and R01NS046400 (SD).

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