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作者

Peijuan Li, Zhangping Sun, Yushu Chen, Zhen Fang, Dongping Yu, Ling Wang, Yanbo Ren, Ping Gong

作者单位

Affiliations ¹ Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to, Shandong First Medical University, Jinan, Shandong, China. ² Department of Emergency, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China. ³ Department of Medical Intensive Care Unit (MICU), Zhongshan Hospital Affiliated to Dalian University, Dalian, Liaoning, China. ⁴ Department of Emergency, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University The First Affiliated Hospital, Southern University of Science and Technology) , Shenzhen, No. 1017, Dongmen North Road, Luohu District, Guangdong, 518020, China. ⁵ Department of Emergency, The Second Affiliated Hospital of Dalian Medical University (Dalian Medical University Cancer Hospital), Dalian, Liaoning, China. ⁶ Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi City, Guizhou Province, China. ⁷ Department of Emergency, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University The First Affiliated Hospital, Southern University of Science and Technology) , Shenzhen, No. 1017, Dongmen North Road, Luohu District, Guangdong, 518020, China. gongp828@sina.cn.

刊名

Molecular neurobiology

年份

2026

卷号

Vol.63 No.1

页码

483

ISSN

1559-1182

关键词

Cardiopulmonary resuscitation Ischemia-reperfusion injury Microglial Phagocytosis eCIRP.

摘要

Cerebral ischemia/reperfusion injury triggers potent neuroinflammatory responses, in which microglial activation and dysregulated phagocytosis may contribute to neuronal damage. Extracellular cold-inducible RNA-binding protein , a damage-associated molecular pattern, has been implicated in postischemic inflammation; however, its role in regulating microglial phagocytosis remains poorly understood. This study employed a porcine model of cardiac arrest/reperfusion and a mouse cellular model of o...更多

Cerebral ischemia/reperfusion injury triggers potent neuroinflammatory responses, in which microglial activation and dysregulated phagocytosis may contribute to neuronal damage. Extracellular cold-inducible RNA-binding protein , a damage-associated molecular pattern, has been implicated in postischemic inflammation; however, its role in regulating microglial phagocytosis remains poorly understood. This study employed a porcine model of cardiac arrest/reperfusion and a mouse cellular model of oxygen-glucose deprivation/reoxygenation in BV2 microglia and N2a neuron to investigate the role of the eCIRP-TREM2 signaling in microglial activation. We evaluated protein expression and direct interaction between CIRP and TREM2 by Western blotting, immunofluorescence, co-immunoprecipitation, and surface plasmon resonance , while assessing phagocytic activity by fluorescent microsphere uptake and synaptic protein expression assays. Both CA/R and OGD/R conditions significantly elevated the levels of CIRP expression and activation of the TREM2-DAP12-Syk-ERK1/2 signaling. Treatment with recombinant human CIRP further increased the expression of microglial activation markers and enhanced phagocytic activity, accompanied by reducing the expression of synaptic proteins. These effects were partially mitigated by CIRBP or TREM2 silencing, or ERK inhibition. Our findings support a novel hypothesis that eCIRP may bind to TREM2 and activate downstream signaling in microglia, enhancing their phagocytic responses in the process of I/R-induced neuronal injury. The eCIRP-TREM2 axis may thus represent a potential therapeutic target for modulating neuroinflammation and preserving neuronal integrity.收起

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期刊