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.
Parasagittal dura (PSD) is located on both sides of the superior sagittal sinus and harbours arachnoid granulations and lymphatic vessels. Efflux of cerebrospinal fluid (CSF) to human PSD has recently been shown in vivo. Here we obtain PSD volumes from magnetic resonance images in 76 patients under evaluation for CSF disorders and correlate them to age, sex, intracranial volumes, disease category, sleep quality, and intracranial pressure. In two subgroups, we also analyze tracer dynamics and time to peak tracer level in PSD and blood. PSD volume is not explained by any single assessed variable, but tracer level in PSD is strongly associated with tracer in CSF and brain. Furthermore, peak tracer in PSD occurs far later than peak tracer in blood, implying that PSD is no major efflux route for CSF. These observations may indicate that PSD is more relevant as a neuroimmune interface than as a CSF efflux route.
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