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Intra-hematomal White Matter Tracts Act As a Scaffold for Macrophage Infiltration After Intracerebral Hemorrhage

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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.

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Funding

NC, YH, RFK, ASP, and GX were supported by grants NS-096917, NS104663, NS106746, NS108042, NS112394, and NS116786 from the National Institutes of Health (NIH).

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Authors and Affiliations

  1. Department of Neurosurgery, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA

    Jingyin Chen, Sravanthi Koduri, Shuhui Dai, Yasunori Toyota, Ya Hua, Neeraj Chaudhary, Aditya S. Pandey, Richard F. Keep & Guohua Xi

  2. Department of Neurosurgery, the 2nd Affiliated Hospital, Zhejiang University, Hangzhou, China

    Jingyin Chen

  3. Department of Radiology, University of Michigan, Ann Arbor, MI, USA

    Neeraj Chaudhary & Aditya S. Pandey

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  1. Jingyin Chen
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  2. Sravanthi Koduri
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  3. Shuhui Dai
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  4. Yasunori Toyota
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  5. Ya Hua
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  8. Richard F. Keep
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  9. Guohua Xi
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Correspondence to Guohua Xi.

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Conflict of Interest

Jingyin Chen, Sravanthi Koduri, Shuhui Dai, Yasunori Toyota, Ya Hua, Neeraj Chaudhary, Aditya S. Pandey, Richard F. Keep, and Guohua Xi declare that they have no conflict of interest.

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Chen, J., Koduri, S., Dai, S. et al. Intra-hematomal White Matter Tracts Act As a Scaffold for Macrophage Infiltration After Intracerebral Hemorrhage. Transl. Stroke Res. 12, 858–865 (2021). https://doi.org/10.1007/s12975-020-00870-5

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  • DOI: https://doi.org/10.1007/s12975-020-00870-5

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