Cerebrospinal fluid can exit into the skull bone marrow and instruct cranial hematopoiesis in mice with bacterial meningitis

Fadi E. Pulous, Jean C. Cruz-Hernández, Chongbo Yang, Ζeynep Kaya, Alexandre Paccalet, Gregory Wojtkiewicz, Diane Capen, Dennis Brown, Juwell W. Wu, Maximilian J. Schloss, Claudio Vinegoni, Dmitry Richter, Masahiro Yamazoe, Maarten Hulsmans, Noor Momin, Jana Grune, David Rohde, Cameron S. McAlpine, Peter Panizzi, Ralph WeisslederDong Eog Kim, Filip K. Swirski, Charles P. Lin, Michael A. Moskowitz, Matthias Nahrendorf

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Interactions between the immune and central nervous systems strongly influence brain health. Although the blood–brain barrier restricts this crosstalk, we now know that meningeal gateways through brain border tissues facilitate intersystem communication. Cerebrospinal fluid (CSF), which interfaces with the glymphatic system and thereby drains the brain’s interstitial and perivascular spaces, facilitates outward signaling beyond the blood–brain barrier. In the present study, we report that CSF can exit into the skull bone marrow. Fluorescent tracers injected into the cisterna magna of mice migrate along perivascular spaces of dural blood vessels and then travel through hundreds of sub-millimeter skull channels into the calvarial marrow. During meningitis, bacteria hijack this route to invade the skull’s hematopoietic niches and initiate cranial hematopoiesis ahead of remote tibial sites. As skull channels also directly provide leukocytes to meninges, the privileged sampling of brain-derived danger signals in CSF by regional marrow may have broad implications for inflammatory neurological disorders.

Original languageEnglish
Pages (from-to)567-576
Number of pages10
JournalNature Neuroscience
Volume25
Issue number5
DOIs
StatePublished - May 2022

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