Abstract
Background: Perihematomal edema (PHE) is a marker of secondary injury in intracerebral hemorrhage (ICH) and is associated with poor clinical outcomes. Microglial and macrophage activation, or their polarization could lead to a pro-inflammatory or anti-inflammatory response in stroke. However, little is known about the association between inflammatory cells and ICH. Thus, we characterized the inflammatory cell response, and assessed its association with parameters such as hematoma, PHE volume, and clinical outcome in patients with acute ICH.Methods: Fifty-two patients with acute ICH were retrospectively enrolled in our study. All patients underwent surgery, and brain tissue from the PHE was acquired. Immunofluorescence staining was performed to evaluate microglia (CD11b+/TMEM119+), macrophages (CD11b+/TMEM119-), and the M1 (MHC+/CD11b+) and M2 (CD206+/CD11b+) phenotypes. The relative PHE (r-PHE) was the main marker for assessing PHE volume. The Wilcoxon test and Spearman correlation analysis were the main statistical analysis methods used.Results: Microglia/macrophages, and their phenotypes were detected within 6 hours after stroke. Microglia and the M2 phenotype were negatively correlated with r-PHE, while macrophages and the M1 phenotype were positively correlated with r-PHE; however, these parameters were not associated with age, sex, or location. There was a positive correlation between the microglia and M2-phenotype levels (r = 0.443, p = 0.001) and between the macrophage and M1-phenotype levels (r = 0.458, p <0.001). Microglia (r = -0.295, p = 0.033) and M2-phenotype (r = -0.384, p = 0.005) levels were negatively correlated with the National Institutes of Health stroke scale (NIHSS) after treatment.Finally, using lasso Poisson regression models, we developed a score for predicting the NIHSS score after treatment. Decision curve analysis showed notable net benefits of this score.Conclusion: Microglial and macrophage activation, and their polarization were significantly associated with r-PHE and clinical outcomes in ICH, and could provide therapeutic insights for PHE management after hemorrhagic stroke.