Functional aspects of cerebrospinal fluid drainage through the cribriform plate
Nagesh C Shanbhag, Jari Jukkola, Marios Kritsilis, Nicholas B Bèchet, Kelley M Swanberg, Chenchen Liu, Xuanhui Liu, Denys Kovalenko, Na Liu, Emily M Johansson, Anja Meissner, Wondossen Sime, Ramin Massoumi, Graham Louw, René In’t Zandt, Iben LundgaardAbstract
Cerebrospinal fluid (CSF) clearance is essential for maintaining brain homeostasis, yet the contribution of the nasal efflux pathway remains incompletely understood. Here, we combined dynamic contrast-enhanced magnetic resonance imaging, optical imaging, and anatomical studies across mice and pigs to characterize the dynamics, regulation, and conservation of nasal CSF drainage. We found that CSF rapidly exited the brain via the cribriform plate, especially during acute volume shifts, and that this route slowed down in aged mice when small molecular weight tracer was used. By contrast, olfactory sensory neuron ablation and amyloid beta1-42 exposure impaired uptake of CSF into the nasal pathway. Notably, signal uptake in superficial cervical lymph nodes appeared distinct from meningeal lymphatic drainage, suggesting functional specialization. Our corroborating findings in pigs further solidify the nasal CSF efflux route as a dynamic, evolutionarily conserved, and potentially targetable pathway with relevance to neuroimmune interactions, aging, and neurodegeneration.