Surface of the vascular plexuses of human cerebral ventricles

The racemose part of vascular plexuses of the lateral ventricles has been studied in fetuses and persons at various age in the scanning and transmissive electron microscopes. In the magistral arteries of the vascular plexuses the neural trunks have been studied. They form the periadventitial plexus with a more complex network of connections in mature persons. The sulci and the elongated folds between them make the relief of the plexus. A rough surface of epitheliocytes has deep craters and irregular protrusions, microvilli, cilia and spherical bodies. The epitheliocytes are arranged in a single layer and connected with each other by means of protoplasmic peduncles. Over the epithelial layer, as single groups, Kolmer cells are situated.     

Appearance and distribution of fetal brain macrophages in mice

Summary A study on the localization of fetal and neonatal brain macrophages of mice from embryonic day 10 (E10) to postnatal day 21 (P21) was carried out immunohistochemically using a monoclonal antibody against a macrophage differentiation antigen (Mac-1) and the labeled avidin-biotin technique. In the central nervous system, the macrophages recognized first were mainly located in the choroid plexuses of the fourth and lateral ventricles at E14. Their number increased at E17–P3 and gradually decreased thereafter. In the cerebral parenchyma, a few macrophages appeared at E14 in the matrix cell layer. They were also detected in the migrating zone at E15, E17 and in the cortical plate at E19. Mapping of positive cells at the stage of neuroblast formation (E15, E17, E19) disclosed the precise distribution of cerebral macrophages. The macrophages that appeared first in the choroid plexuses at E15 may be derived from the subarachnoid vessels, which extend into the stroma of the choroid plexuses when the matrix cell layer invaginates into the lateral ventricle to form the choroid plexuses. Almost all of the macrophages recognized in the cerebral parenchyma disappeared at P9 when the cytoarchitecture seemed to be completed. In the cerebellum, which develops later than the cerebrum, macrophages appeared after birth and were located mainly in the internal granular layer. The brain macrophages always appeared in the regions where cell proliferation and brain remodeling are most active at each stage. These findings suggest that fetal and neonatal brain macrophages may play an important role in scavenging degenerated cells and cell debris during histogenesis of the central nervous system.     

The hypothalamo-choroidal tract

Neurosecretory pathways were examined in normal male rats by the use of the immunoperoxidase technique for the localization of neurophysin in Bouin-fixed, deparaffinized sections. Using this technique two projections of extrahypothalamic neuorosecretory fibers can be traced to the sites of origin of the choid plexuses of both horns of the lateral ventricles. Neurophysin-containing axons originating primarily from the paraventricular field course dorsolaterad to enter the choroid fissure of the dorsal horn. A caudally direced group of fibers course ventrolaterad to enter the ventral horn choroid fissures. The supraoptic nuclear field is the primary contributor to the latter group. Scattered neurosecretory neurons are found in association with both pathways, usually in contact with blood vessels supplying the choroid plexuses, or in the telencephalic subependymal stroma. Neurosecretory fibers and terminals occur within the choroid fissures and juxtaventricular neuropil. The neurosecretory terminals in the choroid fissures appear as Herring-body type neurohemal organs; in the neuropil they appear as punctate peri-neuronal desities suggestive of synaptic contacts. Thes morphologic findings are discussed in relation to reports indicating the presence of antidiuretic, vasopressin-like activity in cerebrospinal fluid and choroid plexus extraxts together with ultrastructural evidence supportive of vasopressin-mediated transchoroidal cerebrospinal fluid absorption. These results and those of others indicated the possible involvement of the neurosecretory system in the regulation of brain interstitial-ventricular cerebrospinal fluid dynamics.     

Fluorescence histochemical study on regional differences in the sympathetic nerve supply of the choroid plexus from various laboratory animals

Summary The adrenergic nerve supply of the choroid plexus in all four ventricles was studied by the Falck-Hillarp histofluorescence technique in nine different species, and the noradrenaline concentration in whole plexus tissue was determined by a radioenzymatic method. The nerve density was usually in the order: third > lateral > fourth ventricular plexuses. Plexuses of the pig and cat possessed the largest number of nerves; the innervation was intermediary in the baboon, guinea-pig, rat, rabbit and hamster, whereas only few fluorescent nerves were found in the cow and mouse plexuses. Sympathetic denervation showed an ipsilateral supply from the superior cervical ganglia to the lateral plexuses and a mixed contribution to the midline plexuses. The total noradrenaline concentration varied between 0.10 and 0.73 ng per mg protein.     

The effect of ventricular volume increase in the amplitude of intracranial pressure

We study the impact of vascular pulse in the cerebrospinal fluid (CSF) pressure measured on the lateral cerebral ventricles, as well as its sensitivity with respect to ventricular volume change. Recent studies have addressed the importance of the compliance capacity in the brain and its relation to arterial pulse abortion in communicating hydrocephalus. Nevertheless, this mechanism is not fully understood. We propose a fluid-structure interaction (FSI) model on a 3?D idealized geometry based on realistic physiological and morphological parameters. The computational model describes the pulsatile deformation of the third ventricle due to arterial pulse and the resulting CSF dynamics inside brain pathways. The results show that when the volume of lateral ventricles increases up to 3.5 times, the amplitudes of both average and maximum pressure values, computed on the lateral ventricles surface, substantially decrease. This indicates that the lateral ventricles expansion leads to a dumping effect on the pressure exerted on the walls of the ventricles. These results strengthen the possibility that communicant hydrocephalus may, in fact, be a natural response to reduce abnormal high intracranial pressure (ICP) amplitude. This conclusion is in accordance with recent hypotheses suggesting that communicant hydrocephalus is related to a disequilibrium in brain compliance capacity.     

Synthesis of transthyretin (pre-albumin) mRNA in choroid plexus epithelial cells, localized by in situ hybridization in rat brain

The sites of synthesis of transthyretin in the brain were investigated using in situ hybridization with [35S]-labeled recombinant cDNA probes specific for transthyretin mRNA. Autoradiography of hybridized coronal sections of rat brain revealed specific cellular localization of transthyretin mRNA in choroid plexus epithelial cells of the lateral, third, and fourth ventricles. Transferrin mRNA was also investigated and, in contrast to transthyretin mRNA, was localized mainly in the lateral ventricles. Our results indicate that substantial synthesis of transthyretin and transferrin mRNA may occur in the choroid plexus.     

A Monte Carlo model for the internal dosimetry of choroid plexuses in nuclear medicine procedures

Choroid plexuses are vascular structures located in the brain ventricles, showing specific uptake of some diagnostic and therapeutic radiopharmaceuticals currently under clinical investigation, such as integrin-binding arginine-glycine-aspartic acid (RGD) peptides. No specific geometry for choroid plexuses has been implemented in commercially available software for internal dosimetry.The aims of the present study were to assess the dependence of absorbed dose to the choroid plexuses on the organ geometry implemented in Monte Carlo simulations, and to propose an analytical model for the internal dosimetry of these structures for ¹⁸F, ⁶⁴Cu, ⁶⁷Cu, ⁶⁸Ga, ⁹⁰Y, ¹³¹I and ¹⁷⁷Lu nuclides. A GAMOS Monte Carlo simulation based on direct organ segmentation was taken as the gold standard to validate a second simulation based on a simplified geometrical model of the choroid plexuses. Both simulations were compared with the OLINDA/EXM sphere model.The gold standard and the simplified geometrical model gave similar dosimetry results (dose difference < 3.5%), indicating that the latter can be considered as a satisfactory approximation of the real geometry. In contrast, the sphere model systematically overestimated the absorbed dose compared to both Monte Carlo models (range: 4–50% dose difference), depending on the isotope energy and organ mass. Therefore, the simplified geometric model was adopted to introduce an analytical approach for choroid plexuses dosimetry in the mass range 2–16 g. The proposed model enables the estimation of the choroid plexuses dose by a simple bi-parametric function, once the organ mass and the residence time of the radiopharmaceutical under investigation are provided.     

Neural connections of the heart and superior vena cava in the rabbit and man

Innervational connections of the heart and the superior vena cava wall have been studied in the rabbit and the man. Besides, series of their embryos, impregnated with silver salts after Cajal-Favorsky have been investigated. Methods of Bielschowsky-Gros, Gomori and Karnovsky-Roots have also been applied. Adrenergic nervous elements have been revealed by means of incubation the slices in 2% solution of glyoxylic acid. Abundant cholinergic and adrenergic nervous plexuses are revealed on the wall of the superior vena cava, they are tightly connected with corresponding plexuses of the heart. Developmental of these nervous connections is followed, when embryogenesis of the cardiac nervous plexuses and large major vessels is studied in serial sections of embryos and fetuses of the rabbit and the man.     

3D Modeling of the Lateral Ventricles and Histological Characterization of Periventricular Tissue in Humans and Mouse

The ventricular system carries and circulates cerebral spinal fluid (CSF) and facilitates clearance of solutes and toxins from the brain. The functional units of the ventricles are ciliated epithelial cells termed ependymal cells, which line the ventricles and through ciliary action are capable of generating laminar flow of CSF at the ventricle surface. This monolayer of ependymal cells also provides barrier and filtration functions that promote exchange between brain interstitial fluids (ISF) and circulating CSF. Biochemical changes in the brain are thereby reflected in the composition of the CSF and destruction of the ependyma can disrupt the delicate balance of CSF and ISF exchange. In humans there is a strong correlation between lateral ventricle expansion and aging. Age-associated ventriculomegaly can occur even in the absence of dementia or obstruction of CSF flow. The exact cause and progression of ventriculomegaly is often unknown; however, enlarged ventricles can show regional and, often, extensive loss of ependymal cell coverage with ventricle surface astrogliosis and associated periventricular edema replacing the functional ependymal cell monolayer. Using MRI scans together with postmortem human brain tissue, we describe how to prepare, image and compile 3D renderings of lateral ventricle volumes, calculate lateral ventricle volumes, and characterize periventricular tissue through immunohistochemical analysis of en face lateral ventricle wall tissue preparations. Corresponding analyses of mouse brain tissue are also presented supporting the use of mouse models as a means to evaluate changes to the lateral ventricles and periventricular tissue found in human aging and disease. Together, these protocols allow investigations into the cause and effect of ventriculomegaly and highlight techniques to study ventricular system health and its important barrier and filtration functions within the brain.     

Adrenergic innervation of the myocardium and skeletal musculature of the rabbit exposed to vibration

Innervation of the myocardium and that of foreleg musculature has been studied in rabbits subjected to the local vibration effect. The point where the vibration is applied is the foreleg, because its nerve plexuses are in the tightest way connected with the cardiac nervous apparatus. For treatment of the sections incubation in 2% solution of glyoxylic acid is used, which is followed with luminescent microscopy. While studying adrenergic nerve plexuses of the right auricle, their luminescent activity is stated to decrease more than by a half. In the ventricles only single perivascular adrenergic nerve plexuses remain. A constant reaction of the plexuses mentioned is revealed not only in the right, but in the left extremity subjected to a direct vibration. Taking into account that the vibrational effect is performed as a generalized action and it embraces the whole skeleton of the animal, it is possible to suggest that the activity of the sympathetic nervous plexuses results in a constant influence of noradrenaline on the wall of blood vessels producing their steady spasmodicity.     

The surface fine structure of the walls of cerebral ventricles and of choroid plexus in cat

Summary The surface of ependymal cells bordering the brain ventricles, and that of the epithelial cells of choroid plexuses of the cat have been investigated by means of the scanning electron microscope. The ventricle walls are entirely covered with very long and numerous cilia and no regional differences have been observed regarding their number and disposition. Among the ciliated cells dome-shaped structures are present, possibly containing nervous elements. The ependymal cells of the third ventricle floor are mainly non ciliated but the surface thereof shows numerous small microvilli. Numerous round formations are present among these cells, their nature being difficult to interpret. Also present on the floor are small cells of triangular shape with long and tortuous protrusions, tentatively identified as small neurons. The choroid plexuses have a typical sinuous structure of long tortuous villi rich in cavities and convolutions. Details of the epithelial cells covering the plexus and their surface organization are also reported.Part of these results were presented to the Septième Congrès International de Microscopie Electronique, Grenoble 1970.     

Complexity and developmental changes in the expression pattern of claudins at the blood–CSF barrier

The choroid plexus epithelium controls the movement of solutes between the blood and the cerebrospinal fluid. It has been considered as a functionally more immature interface during brain development than in adult. The anatomical basis of this barrier is the interepithelial choroidal junction whose tightness has been attributed to the presence of claudins. We used quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry to identify different claudins in the choroid plexuses of developing and adult rats. Claudin-1, -2, and -3 were highly and selectively expressed in the choroid plexus as compared to brain or parenchyma microvessels and were localized at epithelial junctions. Claudin-6, -9, -19, and -22 also displayed a previously undescribed choroidal selectivity, while claudin-4, -5, and -16 were enriched in the cerebral microvessels. The choroidal pattern of tight junction protein expression in prenatal brains was already complex and included occludin and zonula occludens proteins. It differed from the adult pattern in that the pore-forming claudin-2, claudin-9, and claudin-22 increased during development, while claudin-3 and claudin-6 decreased. Claudin-2 and claudin-11 presented a mirror image of abundance between lateral ventricle and fourth ventricle choroid plexuses. Imunohistochemical analysis of human fetal and postnatal brains for claudin-1, -2, and -3 demonstrated their early presence and localization at the apico-lateral border of the choroid plexus epithelial cells. Overall, choroidal epithelial tight junctions are already complex in developing brain. The observed differences in claudin expression between developing and adult choroid plexuses may indicate developmental differences in selective blood–cerebrospinal fluid transport functions.     

Embryonal development and the structure of the intermesenteric plexus in humans and various mammals

The intermesenteric plexus is an independent formation, it is connected with other plexuses in the abdominal and pelvic cavities and participates in innervation of organs. In the species investigated (mole, rat, cat, dog, man) connections between the intermesenteric and other vegetative plexuses in the abdominal and pelvic cavities vary according to their amount and complexity, they are most abundant and complex in man. In the latter the plexus is also mostly rich in neuro-fibrillar and neuro-cellular elements. In the intermesenteric plexus of the man and the animals studied there is a rather big part of vegetative ganglia, which can be considered as peripheral centers of the internal abdominal organs innervation.     

Neuron-specific enolase and S-100 protein immunohistochemistry for defining the structure and topographical relationship of the different enteric nerve plexuses in the small intestine of the pig

Summary The morphological and topographical features of the intramural enteric nervous system in the small intestine of the pig has been studied on whole mounts by means of neuron-specific enolase (NSE) and S-100 protein immu-nohistochemistry. A clear visualization of the myenteric plexus allows the recognition of its characteristic morphology, including the thin tertiary plexus coursing within the smooth muscle layers. In the tela submucosa two ganglionated plexuses, each with its own specific characteristics, can clearly be demonstrated: (1) the plexus submucosus externus (Schabadasch) located near the inner surface of the circular muscle layer at the abluminal side of the submucosal vascular arcades, and (2) the plexus submucosus internus (Meissner) close to the outer surface of the lamina muscularis mucosae at the luminal side of the submucosal vascular arcades. Due to the possibility to trace clearly the perivascular plexuses of these vascular arcades by use of immunohistochemical techniques with antibodies to NSE and S-100 protein, the two submucosal nerve plexuses can be demonstrated with exceptional clarity. This is the first report of an investigation of the intramural nerve plexuses of the small intestine of the pig using the NSE and S-100 immunostaining methods, which is sufficiently detailed to substantiate the characteristic topography and structure of the two submucosal plexuses and their relation to the smooth muscle layers and perivascular plexuses. The level of NSE immunoreactivity for enteric neurons displays great variation, a substantial proportion of the type-II neurons appearing strongly stained. Although little is known of the specific function of these enzymes, proposals are discussed.     

Computational modeling of the mechanical behavior of the cerebrospinal fluid system

A computational fluid dynamics (CFD) model of the cerebrospinal fluid system was constructed based on a simplified geometry of the brain ventricles and their connecting pathways. The flow is driven by a prescribed sinusoidal motion of the third ventricle lateral walls, with all other boundaries being rigid. The pressure propagation between the third and lateral ventricles was examined and compared to data obtained from a similar geometry with a stenosed aqueduct. It could be shown that the pressure amplitude in the lateral ventricles increases in the presence of aqueduct stenosis. No difference in phase shift between the motion of the third ventricle walls and the pressure in the lateral ventricles because of the aqueduct stenosis could be observed. It is deduced that CFD can be used to analyze the pressure propagation and its phase shift relative to the ventricle wall motion. It is further deduced that only models that take into account the coupling between ventricles, which feature a representation of the original geometry that is as accurate as possible and which represent the ventricle boundary motion realistically, should be used to make quantitative statements on flow and pressure in the ventricular space.     

Distribution and characterization of endozepine-like immunoreactivity in the central nervous system of the frog Rana ridibunda.

The localization of endozepine-like immunoreactivity in the brain of the frog Rana ridibunda was investigated by indirect immunofluorescence, using an antiserum against synthetic rat octadecaneuropeptide (ODN). A specific immunoreaction was detected in ependymal cells lining the ventricular system of the brain and in circumventricular organs. Numerous immunoreactive cells were found covering the walls of the lateral ventricles in the telencephalon, as well as in the diencephalic and mesencephalic ventricles. In the hypothalamus, both the preoptic nucleus and the infundibular region showed numerous immunopositive cells. Ependymal cells lining the rhomboencephalic fourth ventricle and the central canal of the spinal cord were also immunoreactive. The concentration of endozepine-like immunoreactivity was measured in various regions of the brain using a sensitive and specific radioimmunoassay for rat ODN. The highest levels of ODN-like immunoreactivity were found in the infundibulum, cerebellum and preoptic area. Reverse phase high performance liquid chromatography and radioimmunoassay quantification were used to characterize endozepines in the frog brain. The elution profiles of the different brain regions revealed four major immunoreactive peaks. The present results demonstrate the presence of peptides immunologically related to the endozepine family in the central nervous system of the frog. The localization of immunoreactive endozepines in ependymal cells suggests that these peptides play important neuromodulatory functions in the amphibian brain.     

Six3 is required for ependymal cell maturation

Ependymal cells are part of the neurogenic niche in the adult subventricular zone of the lateral ventricles, where they regulate neurogenesis and neuroblast migration. Ependymal cells are generated from radial glia cells during embryonic brain development and acquire their final characteristics postnatally. The homeobox gene Six3 is expressed in ependymal cells during the formation of the lateral wall of the lateral ventricles in the brain. Here, we show that Six3 is necessary for ependymal cell maturation during postnatal stages of brain development. In its absence, ependymal cells fail to suppress radial glia characteristics, resulting in a defective lateral wall, abnormal neuroblast migration and differentiation, and hydrocephaly.     

Computer ranking of the sequence of appearance of 40 features of the brain and related structures in staged human embryos during the seventh week of development

The sequence of events in the development of the brain in human embryos, already published for stages 8-17, is here continued for stages 18 and 19. With the aid of a computerized bubble-sort algorithm, 58 individual embryos were ranked in ascending order of the features present. The increasing structural complexity provided 40 new features in these two stages. The chief characteristics of stage 18 (approximately 44 postovulatory days) are rapidly growing basal nuclei; appearance of the extraventricular bulge of the cerebellum (flocculus), of the superior cerebellar peduncle, and of follicles in the epiphysis cerebri; and the presence of vomeronasal organ and ganglion, of the bucconasal membrane, and of isolated semicircular ducts. The main features of stage 19 (approximately 48 days) are the cochlear nuclei, the ganglion of the nervus terminalis, nuclei of the prosencephalic septum, the appearance of the subcommissural organ, the presence of villi in the choroid plexuses of the fourth and lateral ventricles, and the stria medullaris thalami.