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CD47 Blocking Antibody Accelerates Hematoma Clearance After Intracerebral Hemorrhage in Aged Rats

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Abstract

Both experimental studies and surgical clinical trials suggest that hematoma clearance is a therapeutic target in intracerebral hemorrhage (ICH). We have investigated effects of CD47, a “don’t eat me” signal expressed on erythrocytes, on hematoma resolution after ICH in young mice. This study expands those findings by examining the effects on a CD47 blocking antibody in aged rats. First, male Fischer 344 rats (18 months old) received an intracaudate injection of 50 μL autologous whole blood or saline. Hematoma features of magnetic resonance imaging (MRI) and neurological deficits were evaluated within 3 days. Second, rats had an intracaudate co-injection of 50 μL autologous blood with either CD47 blocking antibody or IgG. MRI was used to quantify hematoma/iron volume, hemolysis, brain swelling, and atrophy at different time points, behavioral tests to assess neurological deficits, and immunohistochemistry to assess brain injury and neuroinflammation. The CD47 blocking antibody significantly promoted hematoma clearance, attenuated brain swelling, hemolysis, and neuronal loss and increased the number of phagocytic macrophages in and around hematoma 3 days after ICH. Moreover, CD47 blockade reduced neuronal loss, brain atrophy, and neurobehavioral deficits at day 28. These results indicate that a CD47 blocking antibody can accelerate hematoma clearance and alleviate short- and long-term brain injury after ICH in aged rats and that it might be a therapeutic strategy for ICH.

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Funding

YH, RFK, and GX were supported by grants NS-090925, NS-096917, NS-106746, and NS-112394 from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Neurosurgery, R5018 BSRB, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA

    Chuanyuan Tao, Richard F. Keep, Guohua Xi & Ya Hua

  2. Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China

    Chuanyuan Tao

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  1. Chuanyuan Tao
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  2. Richard F. Keep
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  3. Guohua Xi
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  4. Ya Hua
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Correspondence to Ya Hua.

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The protocols for the animal use were approved by the University of Michigan Institutional Animal Care and Use Committee.

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All institutional and national guidelines for the care and use of laboratory animals were followed.

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Tao, C., Keep, R.F., Xi, G. et al. CD47 Blocking Antibody Accelerates Hematoma Clearance After Intracerebral Hemorrhage in Aged Rats. Transl. Stroke Res. 11, 541–551 (2020). https://doi.org/10.1007/s12975-019-00745-4

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  • DOI: https://doi.org/10.1007/s12975-019-00745-4

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