Microglial CX3CR1 required for M2 polarization and recovery after intracerebral hemorrhage (INC5P.322)

Intracerebral hemorrhage (ICH) occurs when a blood vessel in the brain ruptures, resulting in the activation of microglia. Upon activation, microglia polarize into a pro-inflammatory, M1 phenotype or an M2 phenotype associated with repair. Microglia and monocyte subsets express the chemokine receptor CX3CR1. CX3CR1-null microglia have been shown to have dysregulated inflammation. We hypothesize that microglial CX3CR1-deficiency promotes dysregulated, M1 microglia that do not aid in repair. C57BL/6 (WT) and CX3CR1GFP/GFP (CX3CR1-null) mice were irradiated and reconstituted with bone marrow from WT mice (CD45.1) to generate bone marrow chimeras (CD45.1→WT or CD45.1→CX3CR1-null). ICH was modeled by injecting 20μl of blood into the right striatum. Behavioral outcomes were measured using gait analysis, cylinder test, and beam walking. Mice were sacrificed 14 days after ICH; perihematomal regions were harvested for intracellular staining. The CD45.1→CX3CR1-null mice display greater neurological deficit 14 days after ICH by cylinder test (p=0.002), beam walking (p=<0.001) and gait analysis (p=0.02). By intracellular staining, WT microglia have produce more for IL-10 (p=0.002) and IL-4 (p=0.0003) than CX3CR1-null microglia. CX3CR1-null microglia have less SIRPα (p=0.02) and higher CD36 expression (p=0.0004) compared to WT microglia. Our results suggest CX3CR1 signaling is necessary for microglia to transition from M1 to M2 and contributes to recovery after ICH.