Progress in the Nature Neuroscience series: CSF contributes to the construction of the immune "firewall" of the brain!

Click on the blue word to focus on us that the meninges and choroid plexus play an important role in brain function as the boundaries of the central nervous system
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The brain has its own immune system: the dura mater and the meninges are rich in immune cell populations; the dura mater contains the lymphatic system, which drains cerebrospinal fluid from the brain through the lymph nodes in the neck
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The bone marrow produces a large number of immune cells every day
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Studies have shown that immune cells in the dura and meninges originate from the adjacent skull and spinal marrow
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Bone marrow-derived immune cells of the skull or spinal cord migrate into the meninges through the cranial tunnel
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The choroid plexus produces approximately 500 ml of cerebrospinal fluid per day in humans, which can be drained by arachnoid villi or along the spinal cord and cranial nerves or by meningeal lymphatic cells
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Two recent papers published in the journal Nature Neuroscience reveal a new pathway for cerebrospinal fluid excretion: cerebrospinal fluid can flow into the skull bone marrow through cranial channels and regulate the immune cell pool
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On May 2, 2022, the research team of Matthias Nahrendorf at Massachusetts General Hospital found that cerebrospinal fluid can directly enter the brain bone marrow microenvironment, enabling bidirectional signaling between the brain and the autoimmune system in the skull bone marrow
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Figure 1: The transport channels of cerebrospinal fluid in the skull.
High-resolution tomography revealed that the surface of the mouse skull was enriched with channels, with less channels in the parietal lobe and higher channel density in the frontal and occipital lobes
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Transmission electron microscopy further revealed that these channels are actually perivascular spaces at the openings of the dural channels that accommodate cerebrospinal fluid transport
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Two-photon microscopy revealed that cerebrospinal fluid can flow into the skull bone marrow through the skull channel
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Streptococcus pneumoniae is the leading cause of bacterial meningitis
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After injecting Streptococcus pneumoniae into the cistern magnum in mice for 2 days, the number of Streptococcus pneumoniae in the cerebrospinal fluid increased by about 10,000 times, and the bacterial content in the blood was very low
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Further through bacterial tracing experiments, it was found that fluorescently labeled Streptococcus pneumoniae was found in the skull bone marrow cavity of encephalitis model mice, and about 75% of the mice had fluorescently labeled bacteria along the channel connecting the dura and the skull, indicating that Streptococcus pneumoniae can travel from the dura mater through the cranial tunnel to the skull bone marrow
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Immunofluorescence experiments revealed a marked increase in the number of hematopoietic progenitor cells in the skull of meningitis mice, but not in the distal tibia
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Another, by Jonathan Kipnis' research team at the University of Washington School of Medicine, revealed that the brain and skull bone marrow communicate via cerebrospinal fluid
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In this paper, after injecting fluorescent ovalbumin into the cisterna magna in the cerebrospinal fluid, it was found that fluorescent protein was present in both the cranial channel and the bone marrow, but not in the bone marrow of the distal tibia, which further indicated that the CSF could directly enter the bone marrow of the skull
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Studies have shown that CSF components remodel the neural stem cell microenvironment through receptor-ligand signaling
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They performed single-cell sequencing of calvarial bone marrow and tibial bone marrow tissue and found down-regulation of calvarial bone marrow hematopoietic stem cell proliferation, monocyte-producing reactive oxygen species genes, and macrophage and myeloid cell differentiation genes
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Further proteomic analysis of CSF revealed that ligand-receptor interactions in monocytes and neutrophils revealed signals rich in leukocyte migration, cell adhesion, and phagocytosis, suggesting that CSF components can promote cranial bone marrow Myeloid cell recruitment and migration processes
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Figure 2: Transplantation of cerebrospinal fluid from mice with spinal cord injury affects the state of the calvarial bone marrow of normal mice An increase in these cells was also seen in the calvarial bone marrow after transplantation of CSF from mice with spinal cord injury, suggesting that CSF components promote myelopoiesis and myeloid cell entry into the meninges
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In general, the brain can directly flow into the skull bone marrow through the cerebrospinal fluid, and through its components play the function of recruiting and migrating immune cells to regulate its own immune response
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[References] 1.
https://doi.
org/10.
1038/s41593-022-01060-22.
https://doi.
org/10.
1038/s41593-022-01029-1 The pictures in the text are from references, click to download the original text : 0502-NN-Cerebrospinal fluid can exit into the skull bone.
pdf0502-NN-Cerebrospinal fluid regulates skull bone marrow.
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