The circumventricular organs: an atlas of comparative anatomy and vascularization.

The circumventricular organs are small sized structures lining the cavity of the third ventricle (neurohypophysis, vascular organ of the lamina terminalis, subfornical organ, pineal gland and subcommissural organ) and of the fourth ventricle (area postrema). Their particular location in relation to the ventricular cavities is to be noted: the subfornical organ, the subcommissural organ and the area postrema are situated at the confluence between ventricles while the neurohypophysis, the vascular organ of the lamina terminalis and the pineal gland line ventricular recesses. The main object of this work is to study the specific characteristics of the vascular architecture of these organs: their capillaries have a wall devoid of blood-brain barrier, as opposed to central capillaries. This particular arrangement allows direct exchange between the blood and the nervous tissue of these organs. This work is based on a unique set of histological preparations from 12 species of mammals and 5 species of birds, and is taking the form of an atlas.

Spatial distribution of Reissner's fiber glycoproteins in the filum terminale of the rat and rabbit.

The subcommissural organ secretes into the third ventricle glycoproteins that condense to form the Reissner's fiber (RF). At the distal end of the central canal of the spinal cord, the RF-glycoproteins accumulate in the form of an irregular mass known as massa caudalis. Antibodies against RF-glycoproteins and a set of lectins were used at the light and electron microscopic level to investigate the spatial distribution of the massa caudalis material in the rat and rabbit filum terminale. In the sacral region of the rat, the central canal presents gaps between the ependymal cells through which RF-glycoproteins spread out. The bulk of massa caudalis material, however, escapes through openings in the dorsal wall of the terminal ventricle. In the rabbit, the massa caudalis is formed within the ependymal canal, at the level of the second coccygeal vertebra, it accumulates within preterminal and terminal dilatations of the central canal, and it escapes out through gaps in the dorsal ependymal wall of the terminal ventricle. The existence of wide intercellular spaces and a large orifice (neuroporous) in the dorsal ependymal wall of the terminal ventricle, and the passage of RF-material through them, appear to be conserved evolutionary features. After leaving the terminal ventricle of the rat and rabbit, RF-glycoproteins establish a close spatial association with the numerous blood vessels irrigating the filum terminale, suggesting that in these species the blood vessels are the site of destination of the RF-glycoproteins escaping from the central canal, thus resembling the situation found in lower vertebrates. When passing from the RF stage to the massa caudalis stage, the rabbit RF-glycoproteins lose their sialic acid residues, exposing galactose as the terminal residue. Since this sialic acid-galactose modification of RF-glycoproteins had also been described in lamprey larvae, it may be regarded as a conserved evolutionary feature associated with the formation of the massa caudalis.

The subcommissural organ.

The subcommissural organ (SCO) is a phylogenetically ancient and conserved structure. During ontogeny, it is one of the first brain structures to differentiate. In many species, including the human, it reaches its full development during embryonic life. The SCO is a glandular structure formed by ependymal and hypendymal cells highly specialized in the secretion of proteins. It is located at the entrance of the aqueduct of Sylvius. The ependymal cells secrete into the ventricle core-glycosylated proteins of high molecular mass. The bulk of this secretion is formed by glycoproteins that would derive from two different precursors of 540 and 320 kDa and that, upon release into the ventricle aggregate, form a threadlike structure known as Reissner's fiber (RF). By addition of newly released glycoproteins to its proximal end, RF grows caudally and extends along the aqueduct, fourth ventricle, and the whole length of the central canal of the spinal cord. RF material continuously arrives at the dilated caudal end of the central canal, known as the terminal ventricle or ampulla. When reaching the ampulla, the RF material undergoes chemical modifications, disaggregates, and then escapes through openings in the dorsal wall of the ampulla to finally reach local blood vessels. The SCO also appears to secrete a cerebrospinal fluid (CSF)-soluble material that is different from the RF material that circulates in the ventricular and subarachnoidal CSF. Cell processes of the ependymal and hypendymal cells, containing a secretory material, terminate at the subarachnoidal space and on the very special blood capillaries supplying the SCO. The SCO is sequestered within a double-barrier system, a blood-brain barrier, and a CSF-SCO barrier. The function of the SCO is unknown. Some evidence suggests that the SCO may participate in different processes such as the clearance of certain compounds from the CSF, the circulation of CSF, and morphogenetic mechanisms.

Evidence for basal secretion in the subcommissural organ of the chicken (Gallus gallus).

The basal region of the subcommissural organ (SCO) was studied in the chicken Gallus gallus. The presence of concentric rough endoplasmic reticulum associated with lipid droplets in the basal processes of the ependymal cells, along with the increase of the lysosomal population, can be interpreted as evident signs of degeneration of the basal processes. The nearly absence of secretory processes ending on the meningeal blood vessels, suggests that the leptomeningeal route is missing. On the contrary, the presence of basal ependymal processes in contact with the hypendymal vessels could indicate that the ependymo-vascular pathway is well developed. In this sense, several structural features suggest a basal secretory mechanism from the SCO-cells: 1) Positive staining with paraldehyde-fuchsin of secretory material in the pericapillar region of hypendymal vessels and in the basal processes which reach the capillary wall; 2) presence of secretory material within the process endfeet in contact with hypendymal capillaries, and 3) existence of labyrinthis of the basal lamina of the capillaries.

Vascular and leptomeningeal projections of the subcommissural organ in reptiles. Lectin-histochemical, immunocytochemical, and ultrastructural studies.

In the snake, Natrix maura, and the turtle, Mauremys caspica, the basal processes of the ependymal cells of the subcommissural organ project toward the local blood vessels and the leptomeninges. These processes and their endings were studied using aldehyde-fuchsin (AF), periodic-acid Schiff (PAS), periodic-acid silver-methenamine (PA-SM), concanavalin A (ConA), wheat germ agglutinin (WGA), immunoperoxidase staining (employing an antiserum against bovine Reissner's fiber; AFRU), and conventional transmission electron microscopy. For the purposes of comparison, the ventricular cell pole was also analyzed. The secretory material located in the ventricular cell pole and that present in ependymal endings had only a few staining properties in common, i.e., affinity for AF, ConA, and AFRU at a dilution of 1:1000. On the other hand, PAS, PA-SM, WGA, and AFRU at a dilution of 1:200,000 stained the apical (ventricular) secretory material but not the secretory material of the ependymal processes. The histochemical features of the secretory material located in the terminals of ependymal processes, as well as the presence at these sites of numerous rough-endoplasmic-reticulum cisternae and secretory granules, suggest that secretory material may be synthesized in these terminals. The probable fate of this material, i.e., release to the perivascular and leptomeningeal spaces or transport to the ventricular cell pole, is discussed.

Spatial and structural interrelationships between secretory cells of the subcommissural organ and blood vessels. An immunocytochemical study.

In 76 specimens (amphibians, reptilians, mammals) belonging to 25 different vertebrate species, the region of the subcommissural organ (SCO) was investigated with the use of a primary antiserum raised against an extract of bovine Reissner's fiber + the immunoperoxidase procedure according to Sternberger et al. (1970). In the SCO of a toad (Bufo arenarum) and several species of reptiles (lacertilians, ophidians, crocodilians), the ependymal cells were the only type of secretory cell displaying vascular contacts, whereas in mammals ependymal and hypendymal cells established intimate spatial contacts with blood vessels. In Bufo arenarum, but especially in the reptilian species examined, the ependymo-vascular relationship was exerted by a population of ependymal cells having a rather constant location within the SCO and projecting to capillaries that showed a remarkably constant pattern of anatomical distribution. In the SCO of mammals the modality and degree of the structural relationships between secretory cells and blood vessels varied greatly from species to species. In the SCO of the armadillo and dog the secretory tissue was organized as a thick, highly vascularized layer with most of the cells oriented toward the capillaries. A rather opposite situation was found in the SCO of New- and Old-World monkeys, where vascular contacts were restricted to a few ependymal cells.

Architecture of the basal region of the subcommissural organ in the brush-tailed possum (Trichosurus vulpecula).

The architecture of the basal region of the subcommissural organ (SCO) and the subjacent neuropil was studied in the brush-tailed possum, Trichosurus vulpecula (Marsupialia). Several structural features suggest that the basal mode of SCO-secretion may be as prominent as the well-established apical secretion. Some of the features that speak in favour of basal secretion are: (1) the existence of deep processes of secretion-laden SCO cells which reach and surround the capillaries in the hypendyma and the subjacent neuropil; (2) the presence of perivascular spaces, some of which may contain a material that resembles the secretory product of the SCO; (3) positive staining by means of paraldehyde-fuchsin of secretory material in the pericapillary zone of vessels in the hypendyma and its corresponding neuropil; (4) presence of labyrinths of the basal lamina of capillaries and associated nerves. The presence of nerve and other cell processes adjacent to the perivascular space, labyrinths and capillary wall suggests discharge into the capillaries of material such as the basal secretory product of the SCO. However, the absence of fenestrae in capillary endothelium in the context of the foregoing observations is enigmatic and speaks against the possibility of a conventional release of secretion. Nevertheless, it is possible that a secretory product containing particles of low molecular weight combined with some specific features of the local capillary endothelium, which facilitate transport, may be critical factors making possible transfer of such product(s) from the SCO to the capillaries.

Fine structural studies on ependymal paracellular and capillary transcellular permeability in the subcommissural organ of the guinea pig.

Morphological investigations on the permeability of intercellular junctions between ependymal cells and between capillary endothelial cells in the subcommissural organ (SCO) of the guinea pig have been carried out using freeze-fracturing and tracer experiments with horseradish peroxidase (HRP). The ependymal junction reveals a moderately developed network of tight junctional strands surrounding the tall ependymal cell. The apical portion of this junctional network tends to form nearly complete strands, whereas the basal portion usually shows irregular, fragmented strands often arranged in hairpin-like structures. The passage of intraventricularly infused HRP is blocked, leaving unstained areas, at the level of membrane fusions. At the same time the lateral intercellular space below the junction is densely stained, probably due to invasion from the basal side through adjacent ordinary ependymal junctions. The SCO capillary endothelium shows a high distribution density of pinocytotic vesicles. Vesicular transport of intravascularly injected HRP is observed, but no HRP penetration occurs through the endothelial junction. The active participation of vesicles in tracer movement is shown in preparations fixed before administration of HRP. Extravasation of this tracer is indicated to some degree in the SCO capillary, but permeability here appears to be comparable to that of ordinary brain capillaries. Accordingly, the SCO ependymal tight junction seems to form an effective barrier not to blood plasma or similar materials but to apically secreted substances, preventing them from spreading back into SCO intercellular spaces.

[Periodically striated structures in the subcommissural organ of Clemmys caspica leprosa (Chelonia, Testudinidae) (author's transl)]. / Periodisch quergestreifte Strukturen im Subkommissuralorgan von Clemmys caspica leprosa (Chelonia, Testudinidae).

On a study of the most rostral part of the optic tectum of Clemmys caspica leprosa a periodically striated structure was detected at the subcommissural organ (SCO). It has been made a detailed analysis about its topographical relationship with vessels and with hypendyma, and also about its own periodical pattern of structure. This finding was also considered on a comparative point of view, keeping in mind the previous observations by some authors upon the rat's SCO and other related findings outside the central nervous system. Finally a functional interpretation is discussed.