Innate immune cells recruited to inflammatory sites have short life spans and originate from the marrow, which is distributed throughout the long and flat bones. While bone marrow production and release of leukocyte increases after stroke, it is currently unknown whether its activity rises homogeneously throughout the entire hematopoietic system. To address this question, we employed spectrally resolved in vivo cell labeling in the murine skull and tibia. We show that in murine models of stroke and aseptic meningitis, skull bone marrow-derived neutrophils are more likely to migrate to the adjacent brain tissue than cells that reside in the tibia. Confocal microscopy of the skull–dura interface revealed myeloid cell migration through microscopic vascular channels crossing the inner skull cortex. These observations point to a direct local interaction between the brain and the skull bone marrow through the meninges.
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The authors thank M. Ericsson (HMS Electron Microscopy Facility) for skull sample preparation, sectioning, and assistance with EM imaging. We acknowledge D. Capen (Center for Systems Biology and Program in Membrane Biology/Division of Nephrology, MGH) for help with interpretation of electron microscopy data. The authors thank the MGH mouse imaging program and the Center for Skeletal Research Core (NIH P30 AR066261) for assistance with imaging. This work was funded in part by grants from the National Institutes of Health (NS084863 and HL139598), the American Heart Association (16SDG30190009), the Cure Alzheimer’s Fund, the Global Research Lab (GRL) program (NRF-2015K1A1A2028228) of the National Research Foundation by the Korean government, and by fellowships from the Netherlands Organisation for Scientific Research (NWO, Rubicon Grant: 835.15.014), the Deutsche Forschungsgemeinschaft (RO5071/1-1), and the MGH Research Scholar program.