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Extracellular CIRP dysregulates microglial efferocytosis in ischemic stroke via the TLR4/miR-155/MafB axis

research square. 2025-07; 
Dmitriy Lapin; Dilara Aylar; Archna Sharma; Ping Wang
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Peptide Synthesis reperfusion. Hemostasis was confirmed and cervical wound closed. Mice were randomly assigned to receive vehicle (Phosphate buffered Saline, PBS) or C23 (GenScript, Piscataway, NJ). Immediately after wound closure, mice were retro-orbitally injected with 0.1 mL vehicle or C23 (8 g/g b.w.) dissolved in PBS. Sham (referred to as eCIRP) was prepared in-house, with quality control measures performed as previously described [ 8 ]. C23 (GRGFSRGGGDRGYGG) was synthesized by GenScript USA Inc. (Piscataway, NJ), purified to > 95% by HPLC, and provided as a lyophilized powder. The peptide was resuspended in sterile PBS at desired concentration Get A Quote

摘要

Background. Ischemic stroke remains a leading cause of mortality and disability worldwide, but efforts to develop efficacious neuroprotective therapy face ongoing challenges. Efferocytosis, the phagocytic clearance of dying cells, by microglia is crucial for limiting neuroinflammation and promoting stroke resolution. Extracellular cold-inducible RNA-binding protein (eCIRP) is an inflammatory mediator which impairs macrophage bacterial phagocytosis in sepsis and radiation injury, but its role in microglial efferocytosis in ischemic stroke has not yet been studied.Results. Using a transient middle cerebral artery occlusion (tMCAO) model of ischemic stroke, we demonstrate that eCIRP is released into the cerebrospi... More

关键词

Ischemic stroke, Neuronal death, Neuroinflammation, eCIRP, Microglia, TLR4/miR-155/MafB axis, Efferocytosis, C23 peptide, Therapeutics