Multinucleated Giant Cells in Experimental Intracerebral Hemorrhage
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ORIGINAL ARTICLE
Multinucleated Giant Cells in Experimental Intracerebral Hemorrhage Jialiang Wei 1,2 & Ming Wang 1 & Chaohui Jing 1 & Richard F. Keep 1 & Ya Hua 1 & Guohua Xi 1 Received: 16 January 2020 / Revised: 10 February 2020 / Accepted: 12 February 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Keywords Intracerebral hemorrhage . Multinucleated giant cells . CD 47 . Clodronate liposomes . Macrophage
Introduction Intracerebral hemorrhage (ICH) is a devastating form of stroke with great morbidity and mortality and no current effective therapy [1]. After an ICH, the hematoma itself causes mechanical disruption and increased intracranial pressure (mass effect), but blood components also cause secondary injury [2, 3]. Prior research has indicated that release of hemoglobin degradation products, such as heme and iron, after hemolysis of the hematoma contributes greatly to secondary injury [4]. While hematoma evacuation might be a method of reducing mass effects and hematoma-related neurotoxicity [5, 6], surgical hematoma evacuation has so far failed to provide definitive improvements in patients [7]. There has, therefore, been interest * Guohua Xi [email protected] 1
Department of Neurosurgery, R5018 BSRB, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA
2
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China
in alternative methods of enhancing hem
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