Abstract
Previous studies have demonstrated the potent anti-inflammatory effects of RvE1 in various diseases, and recent research has shown that it can also promote macrophage phagocytosis. Given that hematoma clearance is crucial for intracerebral hemorrhage (ICH) treatment, while neuroinflammation significantly influences secondary injury, we hypothesize that RvE1/ChemR23 activation, by modulating the polarization of macrophages/microglia, promotes hematoma resolution and alleviates neuroinflammatory responses after ICH. A total of 125 WT C57BL/6 and 67 ChemR23-/- male mice were used. Western blot and immunofluorescence staining assessed the temporal and spatial expression of ChemR23 after ICH. T2WI, T2*WI and behavioral tests were obtained to assess the protective effect of the RvE1/ChemR23 pathway in ICH. Additionally, co-staining of M1 (iNOS) or M2 polarization (Arg-1) markers with Iba-1 was used to explore the polarization status of macrophages/microglia in the perihematomal region. Finally, Akt phosphorylation was validated as a downstream mediator of the RvE1/ChemR23 pathway using an Akt inhibitor. ChemR23 is mainly expressed in activated microglia and infiltrating macrophages, with expression peaking 5-7 days post-ICH. Activation of the RvE1/ChemR23 pathway promotes hematoma resolution, reduces brain edema, and improves neurological deficits in ICH. These effects are likely mediated by promoting M2 polarization of macrophages/microglia after ICH. Furthermore, the use of an Akt inhibitor can counteract the protective effects of RvE1 in ICH. Our study provides the first evidence of the protective role of RvE1/ChemR23 signaling in ICH. This pathway might offer novel therapeutic targets for the clinical management of ICH.
Published Version
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