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

CD47 阻断加速血液清除并减轻实验性蛛网膜下腔出血后的早期脑损伤

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作者: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

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.

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.

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.

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