Ultrastructural morphology of the olfactory pathway for cerebrospinal fluid drainage in the rabbit

Abstract

Previous physiological studies indicate that the olfactory region serves as a major pathway for cerebrospinal fluid (CSF) drainage into the lymphatic system. The present study was undertaken to determine the ultrastructural characteristics of this egress route. New Zealand White rabbits received a single bolus injection of the tracer ferritin (MW 400,000) into both lateral ventricles in such a manner as not to raise the intraventricular pressure above the normal level. The animals were sacrificed via intracardiac perfusion of fixative between less than 12 minutes and 4 hours following injection. The cribriform region was removed en bloc, decalcified, sectioned coronally, and prepared for light and electron microscopic examination. The arachnoid, dura, and periosteum surrounding the fila olfactoria passing through the cribriform plate merge together and form the perineurium, which consists of multiple layers of loosely overlapping cells with widely separated junctions and few vesicles. The perineurium surrounding the olfactory filaments at the superficial submucosal level is only one cell thick. The subarachnoid space freely communicates with the perineural space surrounding each filament. No morphological barrier between the perineural space and the loose submucosal connective tissue was identified. Whether or not the perineurium was multi- or single-layered, ferritin was noted in abundance between the loosely overlapping perineural cells and in the submucosal connective tissue. The distribution of ferritin at 12 minutes was similar to that at 4 hours; however, the quantity of ferritin was increased at 4 hours. These results indicate that no significant barrier to CSF drainage is present at the rabbit cribriform region and that CSF reaches the submucosal region rapidly via open pathways.

Olfactory System Involvement in Natural Scrapie Disease

“…5). Studies of ONP ultrastructure at the level of the lamina cribrosa in sheep in particular are lacking, but such descriptions have been made for rabbits (13) and rats (12,60). According to these reports, the olfactory nerves are enveloped along their entire length by olfactory ensheathing cells (OECs) that accompany the olfac- tory fascicules' route toward the olfactory bulb (12), constituting the innermost layer of the ONP.…”

“…The junctions between the fibroblasts of the perineurium are spaced widely apart but are of the tight junction type (13), which is known to restrict the passage of molecules through the spaces between cells. Moreover, the presence of a basal lamina around the OECs abutting the olfactory nerves is an additional feature that may contribute to preventing the uptake of molecules, even PrP Sc , by the underlying ORNs.…”

“…According to previous studies (12,13,23,60), the perineurial cells abutting the olfactory fascicles at the level of ethmoidal lamina cribrosa are an extension of the meninges which pass through the foramina and surround the traversing fila olfactoria (Fig. 5).…”

Pathogens Penetrating the Central Nervous System: Infection Pathways and the Cellular and Molecular Mechanisms of Invasion

“…The mechanisms by which N. meningitidis may travel along the olfactory nerve pathway to invade the nerve fiber layer of the olfactory bulb, the meninges, and CSF are also unknown. The meninges and the subarachnoid space extend over the cribriform plate and further into the olfactory foramen, where the olfactory nerves pass through the cribriform plate (338,339). Bacteria traveling along the olfactory pathway may potentially invade the meninges after traversing the cribriform plate, and subsequently enter the CSF.…”

Cerebrospinal Fluid Reabsorption

“…Other investigators were also able to demonstrate the significance of the lymphatic system as a CSF drainage pathway [4, 10, 30], Bradbury and Westrop [3] believed that more than a third of the CSF might drain into the lymphatic system in rabbits and sheep, and McComb et al [28] found more than 67% of CSF tracer in the lymphatic system of rabbits after a 4-hour perfusion. Subsequent studies from McComb's laboratory demon strated similar findings in cats and showed in the rabbit that this outflow pathway functions through an open-chan nel mechanism with no morphological barrier [16,29], In cats undergoing subarachnoid perfusion of artificial CSF containing horseradish peroxidase (HRP), Butler [5] demonstrated HRP in dural vessels believed to be 'initial lymphatics'. These ultrastrucutral changes occurred at steady state pressures of 175-250 mm H2O, by allowing access of the HRP to these presumed lymphatic chan nels.…”