CD47 Blockade Accelerates Blood Clearance and Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage

AimsSubarachnoid hemorrhage (SAH) is a devastating stroke subtype. Following SAH, erythrocyte lysis contributes to cell death and brain injuries. Blockage of the anti-phagocytic receptor Cluster of Differentiation 47 (CD47) enhances phagocyte clearance of erythrocytes, though it has not been well-st...

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Main Authors: Chao-ran Xu, Jian-ru Li, Shao-wei Jiang, Liang Wan, Xin Zhang, Lei Xia, Xu-ming Hua, Shi-ting Li, Huai-jun Chen, Xiong-jie Fu, Chao-hui Jing
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-02-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.823999/full
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author Chao-ran Xu
Jian-ru Li
Shao-wei Jiang
Liang Wan
Xin Zhang
Lei Xia
Xu-ming Hua
Shi-ting Li
Huai-jun Chen
Xiong-jie Fu
Chao-hui Jing
author_facet Chao-ran Xu
Jian-ru Li
Shao-wei Jiang
Liang Wan
Xin Zhang
Lei Xia
Xu-ming Hua
Shi-ting Li
Huai-jun Chen
Xiong-jie Fu
Chao-hui Jing
author_sort Chao-ran Xu
collection DOAJ
description AimsSubarachnoid hemorrhage (SAH) is a devastating stroke subtype. Following SAH, erythrocyte lysis contributes to cell death and brain injuries. Blockage of the anti-phagocytic receptor Cluster of Differentiation 47 (CD47) enhances phagocyte clearance of erythrocytes, though it has not been well-studied post-SAH. The current study aims to determine whether anti-CD47 treatment can enhance blood clearance after experimental SAH.MethodsThe prechiasmatic blood injection model of SAH was used in mice. Mice were either treated with the CD47-blocking antibody or IgG as control. The effect of the anti-CD47 antibody on blood clearance and neurological function following SAH was determined. Neuroinflammation and neuronal injury were compared between the treatment and control samples on day 1 and day 7 after SAH using flow cytometry, immunofluorescence, Fluoro-Jade C, and Nissl staining, RT-PCR, and Western blot analysis.ResultsCD47-blocking antibody sped-up blood clearance after SAH, and resulted in less neuronal injury and neurological deficits than control samples. Microglia played a role in the anti-CD47 blockade. Following SAH Following SAH, CD47 antibody-treated mice had less neuroinflammation and lower levels of apoptosis compared to controls and both one and 7 days.ConclusionsCD47 antibody treatment has a neuroprotective effect following SAH, by increasing blood clearance rate and reducing brain injury. These findings suggest CD47 antibody treatment may improve SAH patient outcomes.
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spelling doaj.art-7c4ba72228f647b6b1cf229d7b3165b42022-12-21T19:29:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-02-011310.3389/fimmu.2022.823999823999CD47 Blockade Accelerates Blood Clearance and Alleviates Early Brain Injury After Experimental Subarachnoid HemorrhageChao-ran Xu0Jian-ru Li1Shao-wei Jiang2Liang Wan3Xin Zhang4Lei Xia5Xu-ming Hua6Shi-ting Li7Huai-jun Chen8Xiong-jie Fu9Chao-hui Jing10Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Emergency, XinHua Hospital, Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, XinHua Hospital, Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, XinHua Hospital, Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, XinHua Hospital, Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, XinHua Hospital, Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, XinHua Hospital, Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Neurosurgery, XinHua Hospital, Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, ChinaAimsSubarachnoid hemorrhage (SAH) is a devastating stroke subtype. Following SAH, erythrocyte lysis contributes to cell death and brain injuries. Blockage of the anti-phagocytic receptor Cluster of Differentiation 47 (CD47) enhances phagocyte clearance of erythrocytes, though it has not been well-studied post-SAH. The current study aims to determine whether anti-CD47 treatment can enhance blood clearance after experimental SAH.MethodsThe prechiasmatic blood injection model of SAH was used in mice. Mice were either treated with the CD47-blocking antibody or IgG as control. The effect of the anti-CD47 antibody on blood clearance and neurological function following SAH was determined. Neuroinflammation and neuronal injury were compared between the treatment and control samples on day 1 and day 7 after SAH using flow cytometry, immunofluorescence, Fluoro-Jade C, and Nissl staining, RT-PCR, and Western blot analysis.ResultsCD47-blocking antibody sped-up blood clearance after SAH, and resulted in less neuronal injury and neurological deficits than control samples. Microglia played a role in the anti-CD47 blockade. Following SAH Following SAH, CD47 antibody-treated mice had less neuroinflammation and lower levels of apoptosis compared to controls and both one and 7 days.ConclusionsCD47 antibody treatment has a neuroprotective effect following SAH, by increasing blood clearance rate and reducing brain injury. These findings suggest CD47 antibody treatment may improve SAH patient outcomes.https://www.frontiersin.org/articles/10.3389/fimmu.2022.823999/fullsubarachnoid hemorrhageerythrocytesmicroglianeuroinflammationmice
spellingShingle Chao-ran Xu
Jian-ru Li
Shao-wei Jiang
Liang Wan
Xin Zhang
Lei Xia
Xu-ming Hua
Shi-ting Li
Huai-jun Chen
Xiong-jie Fu
Chao-hui Jing
CD47 Blockade Accelerates Blood Clearance and Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage
Frontiers in Immunology
subarachnoid hemorrhage
erythrocytes
microglia
neuroinflammation
mice
title CD47 Blockade Accelerates Blood Clearance and Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage
title_full CD47 Blockade Accelerates Blood Clearance and Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage
title_fullStr CD47 Blockade Accelerates Blood Clearance and Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage
title_full_unstemmed CD47 Blockade Accelerates Blood Clearance and Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage
title_short CD47 Blockade Accelerates Blood Clearance and Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage
title_sort cd47 blockade accelerates blood clearance and alleviates early brain injury after experimental subarachnoid hemorrhage
topic subarachnoid hemorrhage
erythrocytes
microglia
neuroinflammation
mice
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.823999/full
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