ArticleMolecular neurobiology2026
Role of eCIRP in Mediating Post-ischemia Microglial Phagocytosis via TREM-2 Receptor: Insights from Porcine and Mouse Cellular Models.
Article in Molecular neurobiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
1 citing paper in PubMed.
- TREM2 in glioma: Reprogramming the immune microenvironment from mechanistic understanding to clinical translation (Review).Molecular medicine reports · 2026Review
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Authors and funding
8 authors.
Funding
Abstract
Cerebral ischemia/reperfusion (I/R) injury triggers potent neuroinflammatory responses, in which microglial activation and dysregulated phagocytosis may contribute to neuronal damage. Extracellular cold-inducible RNA-binding protein (eCIRP), 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 (CA/R) and a mouse cellular model of oxygen-glucose deprivation/reoxygenation (OGD/R) 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 (SPR), 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 (rhCIRP) 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.
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Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.