The Rapid Invasion of the Body Through the Olfactory Mucosa

Abstract

Clark (1) in 1929 described the introduction of Prussian blue into the nasal cavities of rabbits to determine the routes by which infectious agents pass from these cavities to the brain. At the earliest time of study, 1 hour after nasal inoculation of the pigment, granules were found between the cells of the olfactory mucosa, but not the respiratory, in the submucosa, the lymphatics and venules, in the perineural sheaths and between the fibers of the olfactory nerve, but not the trigeminal, and within the subarachnoid space about the olfactory bulbs. He demonstrated that the perineural spaces of the olfactory nerve are continuous with the subarachnoid space and considered that the granules had reached the olfactory bulbs mainly by passage along the perineural spaces. To account for this migration he postulated a centripetal current in these spaces. He found no evidence of direct communication between the perineural or subarachnoid spaces and the nasal lymphatics and did not determine the method by which the pigment penetrates the mucosa nor the shortest interval in which granules can reach the intracranial cavity.These essential findings have been confirmed by Olitsky and Cox (2) in experiments with mice. Moreover we (3, 4) have shown that pneumococci instilled intranasally in mice pass rapidly through the mucosal surfaces, including tl~ose of the nose, to reach the peripheral blood within 2 minutes. We also, in repeating the tests with Prussian blue in mice, have found (5) that absorption is very rapid, taking place chiefly by way of the olfactory cells, and that within 2 minutes pigment has passed into lymphatics and blood vessels, into perineural 303

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

“…At this time point, bacteria were not isolated from the blood, effectively excluding a hematogenous route of CNS invasion. At 2 min postinfection, pneumococci were observed between the sustentacular cells of the olfactory epithelium, within the perineural space of the olfactory nerve, and within the subarachnoid space (329). Similar findings were reported by van Ginkel et al, who demonstrated that intranasally delivered S. pneumoniae (strain EF3030) could be recovered from nasal washes, the olfactory nerve and epithelium, and the olfactory bulb at 24 h postinfection in CBA/CAHN/xid mice (330).…”

“…pneumoniae. Early studies by Rake demonstrated that S. pneumoniae rapidly enters the olfactory bulb in Swiss mice following intranasal inoculation (329). Remarkably, pneumococci were isolated from the olfactory bulbs of the brain at 1 min postinfection.…”

Nose-to-Brain Transport Pathways of Wheat Germ Agglutinin Conjugated PEG-PLA Nanoparticles

“…The two pathways are collectively called olfactory pathway, which have been confirmed by many studies. For example, Prussian blue was used to visualize the olfactory pathways after intranasal administration to rabbits and mice (7,8). The dye was observed in the olfactory mucosa and the perineural sheaths of the olfactory nerve, indicating that absorption across the epithelium was mainly associated with the olfactory cells (8).…”

“…For example, Prussian blue was used to visualize the olfactory pathways after intranasal administration to rabbits and mice (7,8). The dye was observed in the olfactory mucosa and the perineural sheaths of the olfactory nerve, indicating that absorption across the epithelium was mainly associated with the olfactory cells (8). Jansson and Bjork (9) visualized the distribution of a 3 kDa fluorescein dextran (FD3) in the olfactory epithelium, the respiratory epithelium, the submucosa, the cribriform plate region and the olfactory bulb following nasal administration to rats using fluorescence microscopy.…”

The Lymphatic System

“…Neither of the dyes used nor the HydrokoIIag, although left in the nOSe for as long as six hours, was found to pass through the cribriform plate and reach the interior of the cranium. Prussian blue, rapidly absorbed from the surface of the olfactory mucosa in mice (8), was found within two minutes in the tissue spaces, in blood and lymph vessels, in the perineural spaces of the olfactory nerve fibers, and in the sub arachnoid space and pia-arachnoid membrane. Horse serum, in stilled into the nose, was never detected in the cervical lymph of cats or rabbits.…”