Claudio Vinegoni, Ph.D. | Cerebrospinal fluid can exit into the skull bone marrow and instruct cranial hematopoiesis in mice with bacterial meningitis

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

Pulous, F. E., Cruz-Hernandez, J. C., Yang, C. B., Kaya, Z., Paccalet, A., Wojtkiewicz, G., Capen, D., Brown, D., Wu, J. W., Schloss, M. J., Vinegoni, C., Richter, D., Yamazoe, M., Hulsmans, M., Momin, N., Grune, J., Rohde, D., McAlpine, C. S., Panizzi, P., Weissleder, R., Kim, D. E., Swirski, F. K., Lin, C. P., Moskowitz, M. A., and Nahrendorf^#, M.

Nature Neuroscience 2022

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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. This manuscript describes a new cerebral spinal fluid exit route via hundreds of skull channels, with the cranial bone marrow as a destination. In meningitis, bacteria hijack this path and alert hematopoietic stem cells residing in the skull marrow.
@article{2022-NN, author= {Pulous, F. E. and Cruz-Hernandez, J. C. and Yang, C. B. and Kaya, Z. and Paccalet, A. and Wojtkiewicz, G. and Capen, D. and Brown, D. and Wu, J. W. and Schloss, M. J. and Vinegoni, C. and Richter, D. and Yamazoe, M. and Hulsmans, M. and Momin, N. and Grune, J. and Rohde, D. and McAlpine, C. S. and Panizzi, P. and Weissleder, R. and Kim, D. E. and Swirski, F. K. and Lin, C. P. and Moskowitz, M. A. and Nahrendorf<sup>#</sup>, M.}, title= {Cerebrospinal fluid can exit into the skull bone marrow and instruct cranial hematopoiesis in mice with bacterial meningitis}, journal= {Nature Neuroscience}, alternatejournal = {Nat. Neurosci.}, year = {2022}, volume = {25}, number = {5}, pages = {567-+}, issn = {1097-6256}, doi = {10.1038/s41593-022-01060-2}, pmcid = {PMC9081225}, pmid= {35501382} }
35501382

PMC9081225

10.1038/s41593-022-01060-2

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. This manuscript describes a new cerebral spinal fluid exit route via hundreds of skull channels, with the cranial bone marrow as a destination. In meningitis, bacteria hijack this path and alert hematopoietic stem cells residing in the skull marrow."

Full citation

For attribution in academic contexts, please cite this work as:

Pulous, F. E., Cruz-Hernandez, J. C., Yang, C. B., Kaya, Z., Paccalet, A., Wojtkiewicz, G., Capen, D., Brown, D., Wu, J. W., Schloss, M. J., Vinegoni, C., Richter, D., Yamazoe, M., Hulsmans, M., Momin, N., Grune, J., Rohde, D., McAlpine, C. S., Panizzi, P., … Nahrendorf^#, M. (2022). Cerebrospinal fluid can exit into the skull bone marrow and instruct cranial hematopoiesis in mice with bacterial meningitis. Nature Neuroscience, 25(5), 567-+. https://doi.org/10.1038/s41593-022-01060-2