Abstract
BackgroundIntracerebral hemorrhage (ICH) is one of the major causes of stroke. After onset of ICH, massive infiltration of macrophages is detected in the peri-hematoma regions. Still, the function of these macrophages in ICH has not been completely elucidated.ResultsIn a collagenase-induced ICH model, CX3CR1+ macrophages accumulated in the peri-hematoma region. Characterization of these macrophages revealed expression of alternatively activated (M2) macrophage markers. In the macrophage-depleted mice, ICH-induced brain lesion volume was larger and neurological deficits were more severe compared to those of control mice, indicating a protective role of these macrophages in ICH. In the ICH-injured brain, mannose receptor-expressing macrophages increased at a delayed time point after ICH, indicating M2 polarization of the brain-infiltrating macrophages in the brain microenvironment. To explore this possibility, bone marrow-derived macrophages (BMDM) were co-cultured with mouse brain glial cells and then tested for activation phenotype. Upon co-culture with glia, the number of mannose receptor-positive M2 macrophages was significantly increased. Furthermore, treatment with glia-conditioned media increased the number of BMDM of M2 phenotype.ConclusionsIn this study, our data suggest that brain-infiltrating macrophages after ICH are polarized to the M2 phenotype by brain glial cells and thereby contribute to recovery from ICH injury.
Highlights
Intracerebral hemorrhage (ICH) is one of the major causes of stroke
Round CX3CR1+ cells, morphologically presumed to be brain-infiltrating activated macrophages, accumulated in the peri-hematoma region, which was further increased on 7 dpi (Fig. 1d and e)
In our effort to elucidate mechanisms of macrophage alternatively activated macrophage (M2) polarization in the ICH brain, we found that gliaderived soluble factors have a tendency to drive M2 polarization of bone marrow-derived macrophages (BMDM)
Summary
Intracerebral hemorrhage (ICH) is one of the major causes of stroke. After onset of ICH, massive infiltration of macrophages is detected in the peri-hematoma regions. Results: In a collagenase-induced ICH model, CX3CR1+ macrophages accumulated in the peri-hematoma region Characterization of these macrophages revealed expression of alternatively activated (M2) macrophage markers. In the ICH-injured brain, mannose receptor-expressing macrophages increased at a delayed time point after ICH, indicating M2 polarization of the brain-infiltrating macrophages in the brain microenvironment. To explore this possibility, bone marrow-derived macrophages (BMDM) were co-cultured with mouse brain glial cells and tested for activation phenotype. Interleukin (IL)-4 and IL-10 stimulation induce “alternatively activated” M2 macrophages that promote tissue healing and angiogenesis [14] These two types of macrophage activations are detected in various neurological injury models. We used a mouse model of collagenase-induced ICH to explore the function and phenotype of braininfiltrating macrophages after hemorrhagic stroke
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