Intra-hematomal White Matter Tracts Act As a Scaffold for Macrophage Infiltration After Intracerebral Hemorrhage
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ORIGINAL ARTICLE
Intra-hematomal White Matter Tracts Act As a Scaffold for Macrophage Infiltration After Intracerebral Hemorrhage Jingyin Chen 1,2 & Sravanthi Koduri 1 & Shuhui Dai 1 & Yasunori Toyota 1 & Ya Hua 1 & Neeraj Chaudhary 1,3 & Aditya S. Pandey 1,3 & Richard F. Keep 1 & Guohua Xi 1 Received: 9 September 2020 / Revised: 15 October 2020 / Accepted: 18 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Intracerebral hemorrhage (ICH) is a stroke subtype with high mortality and severe morbidity. Hemorrhages frequently develop within the white matter, but whether white matter fibers within the hematoma survive after ICH has not been well studied. The current study examines whether white matter fibers persist in the hematoma after ICH, fibers that might be impacted by evacuation, and their relationship to macrophage infiltration in a porcine model. Male piglets had 2.5 ml blood with or without CD47 blocking antibody injected into the right frontal lobe. Brains were harvested from 3 days to 2 months after ICH for brain histology. White matter fibers were detected within the hematoma 3 and 7 days after hemorrhage by brain histology and myelin basic protein immunohistochemistry. White matter still remained in the hematoma cavity at 2 months after ICH. Macrophage scavenger receptor-1 positive macrophages/microglia and heme oxygenase-1 positive cells infiltrated into the hematoma along the intra-hematomal white matter fibers at 3 and 7 days after ICH. Treatment with CD47 blocking antibody enhanced the infiltration of these cells. In conclusion, white matter fibers exist within the hematoma after ICH and macrophages/microglia may use such fibers as a scaffold to infiltrate into the hematoma and aid in hematoma clearance. Keywords Intracerebral hemorrhage . Microglia/macrophages . Phagocytosis . White matter
Introduction Spontaneous intracerebral hemorrhage (ICH) affects four million patients worldwide each year [1]. It is the second most common cause of stroke and is associated with high mortality and severe morbidity [2]. Mass effect associated with the hematoma and clot components released into surrounding cerebral tissues contribute to brain injury following ICH [3–6]. The initial injury occurs within minutes to hours of the ICH and is primarily induced by rapidly progressive mass effect leading to decline in cerebral perfusion pressure as well as mechanical injury to surrounding cerebral tissue [7, 8]. * Guohua Xi [email protected] 1
Department of Neurosurgery, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA
2
Department of Neurosurgery, the 2nd Affiliated Hospital, Zhejiang University, Hangzhou, China
3
Department of Radiology, University of Michigan, Ann Arbor, MI, USA
Following the initial injury, cellular debris and clot components initiate secondary injury that takes place over days to weeks [7–9]. There are currently two major forms of hematoma removal, surgical evacuation, and endogenous clot reabsorption. With respect to surgi
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