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Published on: July 29, 2019
Molecular trans-dural efflux to skull bone marrow in humans with CSF disorders
Geir Ringstad1, Per Kristian Eide2,3
1Department of Radiology, Oslo University Hospital-Rikshospitalet, Pb 4950 Nydalen, N-0424 Oslo, Norway.
Abstract:
Dural sinuses were recently identified as a hub for peripheral immune surveillance of brain-derived antigens cleared through CSF. However, animal studies have also indicated that substances and cells may enter the intracranial compartment directly from bone marrow. We used MRI and a CSF tracer to investigate in vivo whether intracranial molecules can move via dura to skull bone marrow in patients with suspicion of CSF disorders. Tracer enrichment in CSF, dural regions and within skull bone marrow was assessed up to 48 h after intrathecal administration of gadobutrol (0.5 ml, 1 mmol/ml) in 53 patients. In participants diagnosed with disease, tracer enrichment within diploe of skull bone marrow was demonstrated nearby the parasagittal dura, nearby extensions of parasagittal dura into diploe, and in diploe of skull bone remote from the dura extensions. This crossing of meningeal and skull barriers suggests that bone marrow may contribute in brain immune surveillance also in humans.
Insights
Brain immune surveillance involves dural sinuses and potentially skull bone marrow. This study shows molecules can travel from cerebrospinal fluid (CSF) to bone marrow in humans, suggesting a role for bone marrow in brain immunity.
Area of Science:
- Neuroimmunology
- Cerebrospinal Fluid (CSF) dynamics
- Medical Imaging
Background:
- Dural sinuses are recognized for immune surveillance of brain antigens cleared via CSF.
- Animal models suggest direct entry of substances and cells from bone marrow into the brain.
- The bidirectional transport between the intracranial compartment and bone marrow in humans remains unclear.
Purpose of the Study:
- To investigate in vivo the movement of intracranial molecules from the dura to skull bone marrow in humans.
- To assess the potential role of skull bone marrow in brain immune surveillance.
Main Methods:
- Magnetic Resonance Imaging (MRI) and a cerebrospinal fluid (CSF) tracer (gadobutrol) were used.
- Intrathecal administration of gadobutrol in 53 patients with suspected CSF disorders.
- Tracer enrichment in CSF, dural regions, and skull bone marrow was assessed up to 48 hours post-injection.
Main Results:
- Tracer enrichment was observed in the diploe of skull bone marrow.
- This enrichment occurred near the parasagittal dura and its extensions into the bone.
- Tracer was also found in bone marrow remote from dural extensions, indicating barrier crossing.
Conclusions:
- Molecules can cross meningeal and skull barriers, moving from the intracranial space to skull bone marrow in humans.
- This suggests that skull bone marrow may play a role in human brain immune surveillance.
- Findings support a potential pathway for immune cell trafficking and antigen presentation between the brain and bone marrow.
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