Abstract
Extra-vascular molecular clearance routes from the brain and cerebrospinal fluid (CSF) remain insufficiently characterized in humans. Animal studies consistently suggest that the cribriform plate and nasal lymphatic vessels are crucial for molecular clearance from CSF. In this study, we aimed to examine human in vivo transport of a CSF tracer from CSF to nasal mucosa. We hypothesised a CSF tracer would enrich in nasal mucosa provided that nasal lymphatic drainage has a significant role in CSF molecular clearance. Consecutive magnetic resonance imaging during 48 h after intrathecal administration of a tracer (gadobutrol) was performed in 24 patients. Despite a strong enrichment of CSF tracer in CSF spaces nearby the cribriform plate, there was no significant enrichment of CSF tracer in nasal mucosa, as measured in superior, medial and inferior turbinates, or in the nasal septum. Therefore, this in vivo study questions the importance of CSF drainage to the human nasal mucosa and emphasizes the need of further human studies.
Highlights
Extra-vascular molecular clearance routes from the brain and cerebrospinal fluid (CSF) remain insufficiently characterized in humans
Induced impairment of meningeal lymphatic vessels suggests that lymphatic drainage is crucial for brain molecular clearance[13,15], indicating a role of lymphatic drainage failure in neurodegeneration caused by the accumulation of neurotoxic molecules in brain tissue
The study included 24 patients examined with consecutive magnetic resonance imaging (MRI) scans before and after intrathecal administration of gadobutrol for work-up of tentative CSF circulation disorders
Summary
Extra-vascular molecular clearance routes from the brain and cerebrospinal fluid (CSF) remain insufficiently characterized in humans. Animal studies consistently suggest that the cribriform plate and nasal lymphatic vessels are crucial for molecular clearance from CSF. Based on studies of a range of animal species, drainage to nasal mucosa via the cribriform plate is consistently shown to represent a major drainage route[1,2,3,4,5,6,7,8,9,10] This route may be hypothesised to be of equal importance in humans. Our group used magnetic resonance imaging (MRI) to demonstrate the accumulation of a MRI contrast agent administered intrathecally in the human parasagittal dura, a tissue possibly serving as an intermediate step towards meningeal lymphatics, paralleled by efflux through neuroforamina at the skull base[16]. We hypothesised that the MRI contrast agent gadobutrol, when administered intrathecally, enriches in nasal mucosa
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