Subarachnoid injection of Microfil reveals connections between cerebrospinal fluid and nasal lymphatics in the non‐human primate

Abstract

Based on quantitative and qualitative studies in a variety of mammalian species, it would appear that a significant portion of cerebrospinal fluid (CSF) drainage is associated with transport along cranial and spinal nerves with absorption taking place into lymphatic vessels external to the central nervous system. CSF appears to convect primarily through the cribriform plate into lymphatics associated with the submucosa of the olfactory and respiratory epithelium. However, the significance of this pathway for CSF absorption in primates has never been established unequivocally. In past studies, we infused Microfil into the subarachnoid compartment of numerous species to visualize CSF transport pathways. The success of this method encouraged us to use a similar approach in the non-human primate. Yellow Microfil was injected post mortem into the cisterna magna of 6 years old Barbados green monkeys (Cercopithecus aethiops sabeus, n = 6). Macroscopic and microscopic examination revealed that Microfil was (1) distributed throughout the subarachnoid compartment, (2) located in the perineurial spaces associated with the fila olfactoria, (3) present within the olfactory submucosa, and (4) situated within an extensive network of lymphatic vessels in the nasal submucosa, nasal septum and turbinate tissues. We conclude that the Microfil distribution patterns in the monkey were very similar to those observed in many other species suggesting that significant nasal lymphatic uptake of CSF occurs in the non-human primate.

The formation of cerebrospinal fluid: Nearly a hundred years of interpretations and misinterpretations

“…Experimental results (Di Chiro, 1964;Orešković et al, 1991;Sato et al, 1972;Sato et al, 1971;Sato and Bering, 1967) also show that CSF is formed outside the brain ventricles (in subarachnoid space). The results also show that CSF absorption occurs not only through villi arachnoidales, but also inside the brain ventricles (Brightman, 1968;Bulat et al, 2008;Cserr, 1971;Dodge and Fishman, 1970;Foley, 1921;Hassin, 1924;Orešković et al, 1991;Wright, 1972), along the nerve roots (Kido et al, 1976), from the subarachnoid space into the lymphatic system (Bradbury, 1981;Brierly and Field, 1948;Dandy, 1929;Johnston et al, 2005;Johnston et al, 2004;Koh et al, 2005;Koh et al, 2006;Weed, 1914), and high intraspinal absorption (Edsbagge et al, 2004).…”

“…Since Shabo and Maxwell (1968) showed that the observed tubular system was probably a consequence of tissue histological preparation, and that the endothelium of arachnoid villi was, in fact, intact (Shabo and Maxwell, 1968), Tripathi and Tripathi (1974) proposed that there are temporary transmesothelial channels which allow the passage of CSF in bulk flow from the subarachnoid space to the venous blood Tripathi and Tripathi, 1974). In addition, there is a large amount of literature which suggests that the significant absorption of CSF (Va) occurs from the subarachnoid space to the lymphatic system (Bradbury, 1981;Brierly and Field, 1948;Dandy, 1929;Johnston et al, 2005;Johnston et al, 2004;Koh et al, 2005;Koh et al, 2006;Weed, 1914). Also, in spite of some other proposed places of CSF absorption (choroid plexuses, brain tissue, etc; see later), in physiological conditions the dural sinuses are still the main place of CSF absorption.…”

Development of hydrocephalus and classical hypothesis of cerebrospinal fluid hydrodynamics: Facts and illusions

“…In addition, there is a large amount of literature which suggests that a significant amount of the absorption of CSF occurs from the subarachnoid space to the lymphatic system (Bradbury, 1981;Brierly and Field, 1948;Dandy, 1929;Johnston et al, 2005;Johnston et al, 2004;Koh et al, 2005;Koh et al, 2006;Weed, 1914). Also, despite some other proposed places (choroid plexuses, brain tissue, etc; see later), in physiological conditions the dural sinuses are still the main place of CSF absorption.…”

“…Additionally, it is believed that the choroid plexuses are also the place of CSF absorption (Dodge and Fishman, 1970;Foley, 1921). Furthermore, there is a large amount of literature which suggests that significant CSF absorption occurs from the SAS to the lymphatic system (Bradbury, 1981;Brierly and Field, 1948;Dandy, 1929;Johnston et al, 2005;Koh et al, 2005;Koh et al, 2006;Weed, 1914). It was also described that CSF has an extrachoroidal origin (Hassin, 1924), and that it is formed, except in the ventricles, within the subarachnoid space (Sato and Bering, 1967;Sato et al, 1971;Sato et al, 1972).…”

New experimental model of acute aqueductal blockage in cats: Effects on cerebrospinal fluid pressure and the size of brain ventricles

“…It is believed that CSF is passively absorbed (under pressure gradient between CSF and blood) through arachnoid villi of the dural venous sinuses. In addition, there is a large amount of literature data which suggests that significant absorption of CSF from subarachnoid space to lymphatic system takes place (Johnston et al, 2004;Johnston et al, 2005;Koh et al, 2006). According to all above, it is generally accepted that CSF should flow unidirectionally (forced by pulsations of vessels) from brain ventricles to subarachnoid space with exchange of various substances (more or less manifested) between CSF and interstitial compartments (Johanson et al, 2008).…”