Development of cerebrospinal fluid absorption sites in the pig and rat: connections between the subarachnoid space and lymphatic vessels in the olfactory turbinates

Abstract

The textbook view that cerebrospinal fluid (CSF) absorption occurs mainly through the arachnoid granulations and villi is being challenged by quantitative and qualitative studies that support a major role for the lymphatic circulation in CSF transport. There are many potential sites at which lymphatics may gain access to CSF but the primary pathway involves the movement of CSF through the cribriform plate foramina in association with the olfactory nerves. Lymphatics encircle the nerve trunks on the extracranial surface of the cribriform plate and absorb CSF. However, the time during development in which the CSF compartment and extracranial lymphatic vessels connect anatomically is unclear. In this report, CSF-lymphatic connections were investigated using the silastic material Microfil and a soluble Evan's blue-protein complex in two species; one in which significant CSF synthesis by the choroid plexus begins before birth (pigs) and one in which CSF secretion is markedly up regulated within the first weeks after birth (rats). We examined a total of 46 pig fetuses at embryonic (E) day E80-81, E92, E101, E110 (birth at 114 days). In rats, we investigated a total of 115 animals at E21 (birth at 21 days), postnatal (P) day P1-P9, P12, P13, P15, P22, and adults. In pigs, CSF-lymphatic connections were observed in the prenatal period as early as E92. Before this time (E80-81 fetuses) CSF-lymphatic connections did not appear to exist. In rats, these associations were not obvious until about a week after birth. These data suggest that the ability of extracranial lymphatic vessels to absorb CSF develops around the time that significant volumes of CSF are being produced by the choroid plexus and further support an important role for lymphatic vessels in CSF transport.

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.…”

Cine Phase-Contrast MR Images Failed to Predict Clinical Outcome Following ETV

“…beyond the basal cisterns and CMJ. [21][22][23] Those CSF absorption devices declined possibly due to lengthy intracranial hypertension, especially in the patient with CSF diversion. 17,20,24 In other words, the previous ETV-treated OHCP might already coexist with "communicating HCP" due to the decrease in CSF absorption even before initial ETV.…”

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).…”