Multinucleated Giant Cells in Experimental Intracerebral Hemorrhage

Macrophage phagocytosis plays an important role in hematoma clearance after intracerebral hemorrhage (ICH). This study examined the characteristics of multinucleated giant cells (MGCs), a group of macrophages with multiple nuclei, in a mouse ICH model. Whether MGCs could be increased by treatment with a CD47 blocking antibody and decreased by treatment with clodronate liposomes were also examined. ICH was induced via autologous blood injection. Male adult C57BL/6 mice in different groups had (1) ICH alone; (2) ICH with anti-CD47 blocking antibody or control IgG; and (3) ICH with anti-CD47 antibody combined with clodronate liposomes or control liposomes. The effect of anti-CD47 antibody on MGC formation was also tested in females. Brains were harvested at days 3 or 7 for brain histology. Many MGCs were found at day 3 post-ICH, but were reduced at day 7. MGCs phagocytosed many red blood cells and were heme oxygenase-1, ferritin, YM-1, and iNOS positive. CD47 blocking antibody injection increased MGC numbers in the peri-hematomal zone and in the hematoma in both sexes. Co-injection of clodronate liposomes depleted MGCs in both the hematoma core and the peri-hematomal area. In conclusion, MGCs represent a macrophage/microglia subtype with strong phagocytosis capacity. MGCs exhibited not only an M2 but also an M1 phenotype and appeared involved in hemoglobin degradation. Anti-CD47 antibody boosted the number of MGCs, which may contribute to enhance hematoma clearance. Understanding the exact roles of MGCs in ICH may reveal novel targets for ICH treatment.