Direct vascular channels connect skull bone marrow and the brain surface enabling myeloid cell migration
Open accessAbstract
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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There is a growing body of evidence from mice that bone marrow-derived myeloid cells can enter the brain during homeostasis.
“There is a growing body of evidence from mice that bone marrow-derived myeloid cells can enter the brain during homeostasis31,32.”
From Clonal hematopoiesis is associated with protection from Alzheimer’s disease (2023) · cites this paper as [32]
The Results section (“Tracking cell origins in different inflammatory sites”; page unavailable) reports skull marrow-derived cells in mouse brain parenchyma after induced meningoencephalitis. That supports entry into the brain, but the paper studies stroke and induced inflammation; it does not establish entry during homeostasis. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSkull bone marrow cells can mount a tailored immune response and supply immune cells to the brain borders and parenchyma post-inflammation.
“They can mount a tailored immune response [387,389]. They supply immune cells to the brain borders and parenchyma post-inflammation [388,389].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [388]
The Introduction and Results report preferential recruitment of skull-marrow neutrophils to the inflamed brain, including cells found in the parenchyma; the Discussion reports leukocytes at the brain surface and in the dura after stroke. The paper does not establish that these cells mount a tailored immune response: its Discussion presents local conditioning of leukocytes as a possibility, not a demonstrated finding. The reported evidence comes from mouse models of acute brain inflammation. (LLM, conf=0.84)
Experimental — accuracy not yet measuredSkull bone marrow cells continuously sample CSF to monitor brain status and can respond to CNS perturbations.
“Skull bone marrow cells continuously sample CSF to monitor brain status by accessing CSF-derived cues and thus can respond to CNS perturbations [388].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [388]
The Results report that skull-marrow neutrophils migrate toward the dura more frequently after stroke or induced brain inflammation. The Discussion proposes that signals from the inflamed brain may reach skull marrow, but the paper does not show that marrow cells continuously sample CSF or access CSF-derived cues to monitor brain status. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThese B cells populate the meninges, where they migrate via specialized vascular channels that circumvent systemic circulation.
“These B cells populate the meninges, a protective triple-layered membrane system surrounding the CNS where they migrate via specialized vascular channels that circum vent systemic circulation [105,106].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [106]
The Results section (‘Direct vascular channels connect skull marrow and the CNS surface’; page unavailable) reports neutrophils moving through skull channels toward the dura after stroke. The Discussion says this route challenges the assumption that recruited leukocytes must first enter systemic circulation. The paper does not establish that B cells populate the meninges or use these channels. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMeningeal B cells are uniquely positioned to interact with CNS-specific antigens, including those linked to Aβ plaques and tau pathology in AD.
“These data suggest that meningeal B cells are uniquely positioned to interact with CNS-specific antigens, including those linked to A β plaques and tau pathology in AD.”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [106]
The Abstract and Discussion describe skull-marrow-derived myeloid cells, particularly neutrophils, migrating toward the brain and meninges. The Discussion mentions Alzheimer’s disease in relation to innate immune cells, but the passages found do not address meningeal B cells interacting with CNS-specific antigens, Aβ plaques, or tau pathology (searched: meningeal B cells, CNS-specific antigens, amyloid, tau). (LLM, conf=0.74)
Experimental — accuracy not yet measured
Diploic veins provide an additional point of entry for immune cells, which can travel directly from the skull bone marrow to the dura mater through 100-μm bone channels.
“These vessels provide an additional point of entry for immune cells, which can travel directly from the skull bone marrow to the dura mater through 100-μm bone channels (95).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [95]
Diploic veins connect bone marrow pockets in the cancellous layer of the skull bone to dural vessels.
“There is also vasculature (diploic veins) that connects bone marrow pockets residing in the cancellous layer of the skull bone to dural vessels.”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [95]
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- Authors
- Herisson, F., Frodermann, V., Courties, G., Rohde, D., Sun, Y., Vandoorne, K., Wojtkiewicz, G. R., Masson, G. S., Vinegoni, C., Kim, J., Kim, D.-E., Weissleder, R., Swirski, F. K., Moskowitz, M. A., & Nahrendorf, M.
- Affiliations
- Harvard University (US)
- Dongguk University (KR)
- Corresponding author
- Nahrendorf, Matthias
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2018-08-27
- Volume
- 21
- Issue
- 9
- Pages
- 1209-1217
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC6148759
- OpenAlex
- W2888160268
- Cited by
- 610
- References
- 37
- Citations by year
- 2026: 104 · 2025: 100 · 2024: 106 · 2023: 90 · 2022: 86 · 2021: 46 · 2020: 30 · 2019: 37 · 2018: 11
- FWCI
- 13.94
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute for Health and Care Research
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (835.15.014)
- National Research Foundation of Korea
- Nature
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL128264, R35HL139598, R01HL131495)
- National Institute of Neurological Disorders and Stroke (R01NS084863)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR066261)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Keywords
- skull bone marrow, myeloid cell migration, neutrophils, stroke, aseptic meningitis, meninges, hematopoietic system, vascular canals, ischemic brain, innate immunity
- MeSH terms
- Adult, Animals, Bone Marrow, Cell Movement, Female, Humans, Inflammation, Male, Meningitis, Aseptic, Mice, Inbred C57BL, Middle Aged, Neutrophils, Skull, Tibia, Tomography, X-Ray Computed, Stroke, Myeloid Cells, Mice
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