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CD47 阻断加速实验性蛛网膜下腔出血后的血液清除并减轻早期脑损伤。

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

机构信息

Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Department of Emergency, XinHua Hospital, Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, China.

出版信息

Front Immunol. 2022 Feb 25;13:823999. doi: 10.3389/fimmu.2022.823999. eCollection 2022.

DOI:10.3389/fimmu.2022.823999
PMID:35281006
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8915201/
Abstract

AIMS

Subarachnoid 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.

METHODS

The 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.

RESULTS

CD47-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.

CONCLUSIONS

CD47 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.

摘要

目的

蛛网膜下腔出血（SAH）是一种破坏性的中风亚型。SAH 后，红细胞溶解导致细胞死亡和脑损伤。阻断抗吞噬受体分化群 47（CD47）可增强吞噬细胞对红细胞的清除，但在 SAH 后尚未得到充分研究。本研究旨在确定抗 CD47 治疗是否可以增强实验性 SAH 后的血液清除。

方法

采用小鼠视交叉前血注射模型进行 SAH。将小鼠分别用 CD47 阻断抗体或 IgG 作为对照进行治疗。用流式细胞术、免疫荧光、Fluoro-Jade C 和尼氏染色、RT-PCR 和 Western blot 分析比较抗 CD47 抗体对 SAH 后血液清除和神经功能的影响。

结果

CD47 阻断抗体加速了 SAH 后的血液清除，与对照样本相比，神经元损伤和神经功能缺损更少。小胶质细胞在抗 CD47 阻断中起作用。SAH 后，与对照组相比，CD47 抗体治疗的小鼠炎症反应较轻，凋亡水平较低，无论是在 1 天还是 7 天。

结论

CD47 抗体治疗对 SAH 具有神经保护作用，通过增加血液清除率和减少脑损伤。这些发现表明 CD47 抗体治疗可能改善 SAH 患者的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a713/8915201/936d4864de4a/fimmu-13-823999-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a713/8915201/82321a22e989/fimmu-13-823999-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a713/8915201/00b5301e0ce8/fimmu-13-823999-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a713/8915201/ef12015f8112/fimmu-13-823999-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a713/8915201/e42b1a155501/fimmu-13-823999-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a713/8915201/f7ab230669da/fimmu-13-823999-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a713/8915201/f76edad1d12a/fimmu-13-823999-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a713/8915201/936d4864de4a/fimmu-13-823999-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a713/8915201/82321a22e989/fimmu-13-823999-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a713/8915201/00b5301e0ce8/fimmu-13-823999-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a713/8915201/ef12015f8112/fimmu-13-823999-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a713/8915201/e42b1a155501/fimmu-13-823999-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a713/8915201/f7ab230669da/fimmu-13-823999-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a713/8915201/f76edad1d12a/fimmu-13-823999-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a713/8915201/936d4864de4a/fimmu-13-823999-g007.jpg

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