Anatomical basis and physiological role of cerebrospinal fluid transport through the murine cribriform plate

Abstract

Cerebrospinal fluid (CSF) flows through the brain, transporting chemical signals and removing waste. CSF production in the brain is balanced by a constant outflow of CSF, the anatomical basis of which is poorly understood. Here, we characterized the anatomy and physiological function of the CSF outflow pathway along the olfactory sensory nerves through the cribriform plate, and into the nasal epithelia. Chemical ablation of olfactory sensory nerves greatly reduced outflow of CSF through the cribriform plate. The reduction in CSF outflow did not cause an increase in intracranial pressure (ICP), consistent with an alteration in the pattern of CSF drainage or production. Our results suggest that damage to olfactory sensory neurons (such as from air pollution) could contribute to altered CSF turnover and flow, providing a potential mechanism for neurological diseases.

A Comparison of the Primary Sensory Neurons Used in Olfaction and Vision

“…The OE and bulb are separated from each other by the ethmoid bone. The ethmoid bone has a specialized zone of small openings, the foramina in the cribriform plate (CP), that allow the OSN axons passage to the interior of the skull (Choi and Goldstein, 2018;Norwood et al, 2019). OSNs are genetically encoded to respond to specific odorants based on the single odorant receptor (OR) they express, the axons of OSN expressing the same OR converge on one to two glomeruli and synapse with mitral and tufted cells within the outer nuclear layer (ONL) of the OB (Buck and Axel, 1991;Ressler et al, 1993;Vassar et al, 1993;Mombaerts et al, 1996).…”

The Cranial Bowl in the New Millennium and Sutherland's Legacy for Osteopathic Medicine: Part 1

“…The exchange mechanism between interstitial fluids and CSF at the level of the perivascular spaces is defined as the glymphatic system (glial cells and lymph) [21]. We know that there are meningeal lymphatic vessels but, probably, they do not have direct exchanges with CSF, if not out of the nervous system [28]. The pathways that CSF follows while exiting the skull are varied.…”

“…The pathways that CSF follows while exiting the skull are varied. From the venous perivascular space, the CSF reaches the olfactory bulb, to enter the perineural space of the olfactory nerve (15%-20% of all the CSF), up to the nasal mucosa, where the CSF will be drained by the lymphatic vessels of the mucosa; from here, the fluid enters the sub-buccal and mandibular lymphatic tracts, up to the cervical and spinal lymphatic nodes [28]. At the base of the skull there are many lymphatic vessels that penetrate the skull, following the exit routes of the cranial and spinal nerves [11].…”

Structural and functional conservation of non-lumenized lymphatic endothelial cells in the mammalian leptomeninges

“…There is some evidence that dorsal dural lymphatic vessels are capable of draining macromolecules from the CSF [5,38]. However, other reports fail to detect CSF drainage into dorsal dural lymphatics and suggest alternative drainage routes, such as along blood vessels or olfactory nerves or within lymphatic vessels that pass through the cribriform plate, or into the ventral dural lymphatics at the base of the skull [1,23,28,31,39,45]. Dorsal dural lymphatics can also transport immune cells from the meninges and modulate T-cell activation during inflammation, and ablation studies of the dorsal dural lymphatics have demonstrated the importance of these vessels in the promotion of neuroinflammatory responses in an animal model of multiple sclerosis [37].…”