Relationship between the saccus endolymphaticus and the fourth ventricle of the brain of the domestic fowl (Gallus gallus f. domestica)

The fine structure of the wall of the SE was determined exactly and its relationship to the cisternae (the evaginations of the roof of the fourth ventricle extending to the SE) was defined. The way in which the cisterna is formed was defined and the development of its fine structure was described by comparing serial sections from 19-day embryos and adult fowls. Like the SE, the cisternae are lodged in the angle between the cerebellum and the medulla oblongata, in the subarachnoid space. The terminal segment of the cisterna lies in the immediate vicinity of the mesenchymal epithelium bordering the basal labyrinth of the SE cells. Collagen trabeculae keep the SE and the cisternae suspended in the subarachnoid space. The cisternae and trabeculae are wrapped in mesenchymal epithelium. The cisterna is avascular and does not communicate with the SE. The cisterna is lined internally with simple squamous epithelium (modified neural epithelium of the roof of the fourth ventricle). The bodies of the cells bulge into the lumen of the cisterna in the region of localization of their nucleus. The epithelium is seated on a pronounced basal lamina. The surface turned towards the subarachnoid space is lined continuously with mesenchymal epithelium without a basal lamina. The cells of the cisternal epithelium are connected by tight junctions of the type of zonulae occludentes and desmosomes. The basal lamina is continuous and distinct. The mesenchymal epithelium of the subarachnoid space has no basal lamina, as on the subarachnoid surface of the SE, the cisternae, the trabeculae, the pia mater and the arachnoidea.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of anatomical fine structure on the flow of cerebrospinal fluid in the spinal subarachnoid space

The lattice Boltzmann method is used to model oscillatory flow in the spinal subarachnoid space. The effect of obstacles such as trabeculae, nerve bundles, and ligaments on fluid velocity profiles appears to be small, when the flow is averaged over the length of a vertebra. Averaged fluid flow in complex models is little different from flow in corresponding elliptical annular cavities. However, the obstacles stir the flow locally and may be more significant in studies of tracer dispersion.     

A mechanical approach to the longitudinal dispersion of gas flowing in human airways

The aim of this work is to contribute to elucidating the mechanism underlying gas mixing in the human pulmonary airways. For this purpose, a particular attempt is made to analyse the fluid mechanical aspects of gaseous dispersion using bolus response methods. The experiments were performed on five normal subjects by injection of 10 cm3 bolus of He, Ar and SF6 into the latter part of the inspired airstream, in such a way that the whole bolus entered the inspiratory flow and was recovered during the following expiration. The results, presented in a logarithmic plot of dimensionless variance (dispersion of the output bolus) against the Peclet number, show that gaseous dispersion is only slightly dependent on the nature of the tracer gas but is strongly related to flow velocity. This is in agreement with the theory of turbulent or disturbed dispersion; however, it seems that Taylor laminar dispersion does not play a significant role in the airways.     

Contribution of upper airway geometry to convective mixing

We investigated the axial dispersive effect of the upper airway structure (comprising mouth cavity, oropharynx, and trachea) on a traversing aerosol bolus. This was done by means of aerosol bolus experiments on a hollow cast of a realistic upper airway model (UAM) and three-dimensional computational fluid dynamics (CFD) simulations in the same UAM geometry. The experiments showed that 50-ml boluses injected into the UAM dispersed to boluses with a half-width ranging from 80 to 90 ml at the UAM exit, across both flow rates (250, 500 ml/s) and both flow directions (inspiration, expiration). These experimental results imply that the net half-width induced by the UAM typically was 69 ml. Comparison of experimental bolus traces with a one-dimensional Gaussian-derived analytical solution resulted in an axial dispersion coefficient of 200-250 cm(2)/s, depending on whether the bolus peak and its half-width or the bolus tail needed to be fully accounted for. CFD simulations agreed well with experimental results for inspiratory boluses and were compatible with an axial dispersion of 200 cm(2)/s. However, for expiratory boluses the CFD simulations showed a very tight bolus peak followed by an elongated tail, in sharp contrast to the expiratory bolus experiments. This indicates that CFD methods that are widely used to predict the fate of aerosols in the human upper airway, where flow is transitional, need to be critically assessed, possibly via aerosol bolus simulations. We conclude that, with all its geometric complexity, the upper airway introduces a relatively mild dispersion on a traversing aerosol bolus for normal breathing flow rates in inspiratory and expiratory flow directions.     

Circulation of marker substances in the cerebrospinal fluid of an amphibian,Rana pipiens

Summary Solutions of fluorescein-labelled dextran or Evans blue-albumin were infused into the lateral cerebral ventricle of Rana pipiens. The subsequent distribution in the cerebrospinal fluid (CSF) was investigated between 2 and 24 h after infusion by freezing and examination of the cut blocks of the head and vertebral column of the stage of a freezing microtome. These marker substances move out of the ventricles into the subarachnoid space at the caudal end of the fourth ventricle and spread rapidly along the subarachnoid space of the spinal cord. The spreading of marker substances is slower into the brain subarachnoid space. When the marker is infused into the subarachnoid space of the forebrain, it becomes distributed throughout the subarachnoid space of the brain and spinal cord but not in the ventricles.Partial clearance of markers from the ventricles takes place within 5 h and total clearance within 8 h. Clearance from the brain and cord subarachnoid space is somewhat slower and can only be detected in experiments lasting 10 h or more. Absorption of the markers from the CSF occurs via the intervertebral foramina of the spinal cord. Fluorescence microscopy of sections of the cord show that the fluorescence leaves the subarachnoid space at the point where the spinal nerves traverse the arachnoid membrane.     

Continuity between the ventricular and subarachnoid cerebrospinal fluid in an amphibian,Rana pipiens

Summary Continuity between the ventricular and subarachnoid cerebrospinal fluid has been investigated in Rana pipiens. The structure of the posterior tela, a deficient membrane situated at the extreme caudal end of the roof of the fourth ventricle, has been studied using whole membrane mounts and by light microscopy of resin embedded tissue. The ependymal component consists of columnar and rounded cells which form a regular syncytium enclosing round and oval fenestrations. Small fenestrations are covered on the subarachnoid side by elongated pial cells and thus do not give total continuity between the fourth ventricle and the subarachnoid space. Large fenestrations, on the other hand, are accompanied by equivalent pial fenestrations giving direct access between the fluid compartments. Towards the caudal end the fenestrations break up and the numbers of ependymal and pial cells decrease, the caudal end itself being characterised by a small remaining clump of ependyma and pia or of pia alone.Flow through the tela has been studied using fluorescein-labelled dextran placed in the intraventricular space. Infusion into the lateral ventricle and subsequent localisation by fluorescence microscopy shows the marker to be in the fourth ventricle, in the fenestrations of the posterior tela and in the subarachnoid space overlying the tela. Infusion of the marker followed by freezing and examination of the cut heads on a freezing microtome, shows fluorescence throughout the ventricular system, in the subarachnoid space adjacent to the posterior tela and also along the dorsal subarachnoid space of the spinal cord.     

Application of fluorescent dextrans to the brain surface under constant pressure reveals AQP4-independent solute uptake

Extracellular solutes in the central nervous system are exchanged between the interstitial fluid, the perivascular compartment, and the cerebrospinal fluid (CSF). The “glymphatic” mechanism proposes that the astrocyte water channel aquaporin-4 (AQP4) is a major determinant of solute transport between the CSF and the interstitial space; however, this is controversial in part because of wide variance in experimental data on interstitial uptake of cisternally injected solutes. Here, we investigated the determinants of solute uptake in brain parenchyma following cisternal injection and reexamined the role of AQP4 using a novel constant-pressure method. In mice, increased cisternal injection rate, which modestly increased intracranial pressure, remarkably increased solute dispersion in the subarachnoid space and uptake in the cortical perivascular compartment. To investigate the role of AQP4 in the absence of confounding variations in pressure and CSF solute concentration over time and space, solutes were applied directly onto the brain surface after durotomy under constant external pressure. Pressure elevation increased solute penetration into the perivascular compartment but had little effect on parenchymal solute uptake. Solute penetration and uptake did not differ significantly between wild-type and AQP4 knockout mice. Our results offer an explanation for the variability in cisternal injection studies and indicate AQP4-independent solute transfer from the CSF to the interstitial space in mouse brain.     

Effects of fluid structure interaction in a three dimensional model of the spinal subarachnoid space

It is unknown whether spinal cord motion has a significant effect on cerebrospinal fluid (CSF) pressure and therefore the importance of including fluid structure interaction (FSI) in computational fluid dynamics models (CFD) of the spinal subarachnoid space (SAS) is unclear. This study aims to determine the effects of FSI on CSF pressure and spinal cord motion in a normal and in a stenosis model of the SAS. A three-dimensional patient specific model of the SAS and spinal cord were constructed from MR anatomical images and CSF flow rate measurements obtained from a healthy human being. The area of SAS at spinal level T4 was constricted by 20% to represent the stenosis model. FSI simulations in both models were performed by running ANSYS CFX and ANSYS Mechanical in tandem. Results from this study show that the effect of FSI on CSF pressure is only about 1% in both the normal and stenosis models and therefore show that FSI has a negligible effect on CSF pressure.     

On the transmission of external pressure fluctuations to the cerebrospinal fluid

A theory has been formulated to explain the manner in which external pressure fluctuations are transmitted to the cerebrospinal fluid (CSF). The theory is based upon a three-compartment model which consists of the cerebral ventricles, the basal cisterns and spinal subarachnoid space, and the cortical subarachnoid space. The external pressure disturbance is represented by a Fourier series summed over the frequency ω. The mathematical analysis leads to a time constant τ which depends upon the compliances of the spinal region and sources of external pressure fluctuations, the rate of CSF absorption and the rate of fluid transfer between compartments. For arterial pulsations where ωτ ? 1, the theory is in accord with the experimental observations that (i) the arterial and CSF pulse waves are nearly identical in shape, and (ii) the amplitude of the CSF pulse wave increases with intracranial pressure. Moreover, it predicts that the amplitude of the wave will be larger in the spinal region than in the ventricles. The theory also accounts for the observation of one per minute pulse waves observed in hydrocephalic patients with decreased absorption rates.     

Bovine pituitary intraglandular colloid: a transport medium

Bovine pituitary intraglandular colloid is formed by the cyclic degeneration of marginal cells lining the intermediate lobe and is housed in the intraglandular lumen (residual lumen). The lumen communicates with the subarachnoid cerebrospinal fluid space by well defined channels. Electrophoresis in acrylamide gel shows bovine pituitary intraglandular colloid as having double protein bands identical to the protein in bovine and human cerebrospinal fluid. These studies demonstrate two distinct bands in the gamma region for colloid, not apparent in the normal bovine or human cerebrospinal fluid due to the low concentration of gamma globulins. We conclude that pituitary colloid, laden with immunoreactive fragments of various pituitary hormones, is discharged from the hypophyseal intraglandular space, directly into the subarachnoid cerebrospinal fluid space.     

Spinal cord central canal of the German shepherd dog: Morphological,histological, and ultrastructural considerations

This study deals with some macroscopical, microscopical, and ultrastructural aspects of the spinal cord central canal of the German shepherd dog. The caudal end of the spinal cord is constituted by the conus medullaris, which may extend to the first sacral vertebra, the terminal ventricle, and the filum terminale. The latter structure is considered as internum (second to third sacral vertebrae) or externum (fifth caudal vertebra), according to its relation to the dura mater. Occasionally, there is a second anchorage which is close to the level of the sixth caudal vertebra. The central canal is surrounded by a ciliated ependymal epithelium, which differs depending upon the levels. The most caudal part of the filum terminale bears a columnar ciliated ependymal epithelium surrounded by two layers of glia and pia mater, which separate the central canal from the subarachnoid space. Microfil injections show a communication between the cavity and the subarachnoid space, as the plastic is able to pass through the ependymal epithelium. At the level of the terminal ventricle there are real separations of the ependymal epithelium, which seem to connect the lumen of the spinal canal with the subarachnoid space. These structures probably constitute one of the drainage pathways of the cerebrospinal fluid. The diameter of the central canal is related to the age of the animal. However, even in very old animals the spinal cord central canal reaches the tip of the filum terminale and remains patent until death. At the ultrastructural level the ependymal cells present villi, located on cytoplasmic projections, cilia, dense mitochondria, and oval nuclei. © 1995 Wiley-Liss, Inc.     

Effect of naloxone administration upon the diurnal concentrations of oxytocin in the cerebrospinal fluid of rhesus and cynomolgus monkeys.

A diurnal pattern in oxytocin concentrations is present in cerebrospinal fluid (CSF) removed from the spinal subarachnoid space of monkeys, with elevated levels occurring in the early light hours. In order to investigate the possible role of endogenous opioid peptides in the generation of this oxytocin rhythm, we administered naloxone (0.4 mg/kg/h x 48 h) to rhesus and cynomolgus monkeys and examined the effects on the diurnal pattern of oxytocin in CSF collected from the lumbar subarachnoid spinal space. Monkeys maintained on jacket/tether/swivel systems and in a 12 h light: 12 h dark cycle (lights on 07.00-19.00 h) were implanted with temporary spinal subarachnoid catheters. CSF was continuously collected from the lumbar subarachnoid space and assayed for oxytocin. Oxytocin concentrations in CSF showed a diurnal variation with peak and nadir concentrations during light and dark hours, respectively. The lumbar CSF concentrations of oxytocin were not significantly different during naloxone vs. saline infusion. Plasma oxytocin concentrations, measured in the same animals, displayed no diurnal variation and were not significantly different during naloxone vs. saline infusion. We conclude that naloxone administration for 48 h does not perturb the diurnal variation in oxytocin concentrations in the CSF of monkeys. Mu opioid receptors are unlikely to be involved in modulating the diurnal rhythm of oxytocin in the CSF of monkeys.     

Transit time dispersion in pulmonary and systemic circulation: effects of cardiac output and solute diffusivity

We present an in vivo method for analyzing the distribution kinetics of physiological markers into their respective distribution volumes utilizing information provided by the relative dispersion of transit times. Arterial concentration-time curves of markers of the vascular space [indocyanine green (ICG)], extracellular fluid (inulin), and total body water (antipyrine) measured in awake dogs under control conditions and during phenylephrine or isoproterenol infusion were analyzed by a recirculatory model to estimate the relative dispersions of transit times across the systemic and pulmonary circulation. The transit time dispersion in the systemic circulation was used to calculate the whole body distribution clearance, and an interpretation is given in terms of a lumped organ model of blood-tissue exchange. As predicted by theory, this relative dispersion increased linearly with cardiac output, with a slope that was inversely related to solute diffusivity. The relative dispersion of the flow-limited indicator antipyrine exceeded that of ICG (as a measure of intravascular mixing) only slightly and was consistent with a diffusional equilibration time in the extravascular space of approximately 10 min, except during phenylephrine infusion, which led to an anomalously high relative dispersion. A change in cardiac output did not alter the heterogeneity of capillary transit times of ICG. The results support the view that the relative dispersions of transit times in the systemic and pulmonary circulation estimated from solute disposition data in vivo are useful measures of whole body distribution kinetics of indicators and endogenous substances. This is the first model that explains the effect of flow and capillary permeability on whole body distribution of solutes without assuming well-mixed compartments.     

Pulmonary arterial transit times

To begin to characterize the pulmonary arterial transport function we rapidly injected a bolus containing a radiopaque dye and a fluorescence dye into the right atrium of anesthetized dogs. The concentrations of the dye indicators were measured in the main pulmonary artery (fluoroscopically) and in a subpleural pulmonary arteriole (by fluorescence microscopy). The resulting concentration vs. time curves were subjected to numerical deconvolution and moment analysis to determine how the bolus was dispersed as it traveled through the arteriole stream tube from the main pulmonary artery to the arteriole. The mean transit time and standard deviation of the transport function from the main pulmonary artery to the arterioles studied averaged 1.94 and 1.23 s, respectively, and the relative dispersion (ratio of standard deviation to mean transit time) was approximately 64%. This relative dispersion is at least as large as those reported for the whole dog lung, indicating that relative to their respective mean transit times the dispersion upstream from the arterioles is comparable to that taking place in capillaries and/or veins. The standard deviations of the transport functions were proportional to their mean transit times. Thus the relative dispersion from the main pulmonary artery to the various arterioles studied was fairly consistent. However, there were variations in mean transit time even between closely adjacent arterioles, suggesting that variations in mean transit times between arteriole stream tubes also contribute to the dispersion in the pulmonary arterial tree.     

The effects of variation in the arterial pulse waveform on perivascular flow

Cerebrospinal fluid (CSF) enters nervous tissues through perivascular spaces. Flow through these pathways is important for solute transport and to prevent fluid accumulation. Syringomyelia is commonly associated with subarachnoid space obstructions such as Chiari I malformation. However, the mechanism of development of these fluid-filled cavities is unclear. Studies have suggested that changes in the arterial and CSF pressures could alter normal perivascular flow. This study uses an idealised model of the perivascular space to investigate how variation in the arterial pulse influences fluid flow. The model used simulated subarachnoid pressures from healthy controls (N = 9), Chiari patients with (N = 7) and without (N = 8) syringomyelia. A parametric analysis was conducted to determine how features of the arterial pulse altered flow. The features of interest included: the timing and magnitude of the peak displacement, and the area under the curve in the phases of uptake and decline. A secondary aim was to determine if the previously observed differences between subject groups were sensitive to variation in the arterial pulse wave. The study demonstrated that the Chiari patients without a syrinx maintained a significantly higher level of perivascular inflow over a physiologically likely range of pulse wave shapes. The analysis also suggested that age-related changes in the arterial pulse (i.e. increased late systolic pulse amplitude and faster diastolic decay), could increase resistance to perivascular inflow affecting solute transport.     

Effect of endothelin-1 receptor antagonist BQ-123 on basilar artery diameter after subarachnoid hemorrhage (SAH) in rats.

Aim of the study was to quantify cerebral vasospasm in rats after subarachnoid hemorrhage (SAH) by morphometric examination of basilar artery and to evaluate the influence of endothelin receptor blocker BQ-123 on basilar artery constriction. The rat cisterna magna (CM) was cannulated and after 7 days SAH was developed by administration of 100 microl autologic, non-heparinized blood to the CM. The sham subarachnoid hemorrhage was developed by intracisternal administration of 100 microl of artificial cerebrospinal fluid. Endothelin receptor blocker BQ-123 was injected into the CM in a dose of 40 nmol diluted in 50 microl of cerebrospinal fluid 20 min. before SAH, and 24h and 48 h after SAH. After perfusion fixation the brains were removed from the skull and histological preparations of basilar artery were done. The internal diameter and wall thickness of basilar arteries was measured by interactive morphometric method. The most severe vasospasm was found in rats after SAH. The presence of numerous infiltrations composed of neutrophils and macrophages correlated with advanced vasospasm (index of constriction 5 times lower than in normal), suggesting the role of other factors participating in the late phase of vasospasms after SAH. Administration of BQ-123 in the late phase after SAH caused the dilatation of basilar artery. Following the administration of BQ-123 in the late phase (48 h after SAH) the basilar artery dilated, its wall became thinner, and the number of leukocyte infiltrations in the subarachnoid space decreased compared to the values after SAH alone.     

The fine structure of the axial organ of the feather star Nemaster rubiginosa (echinodermata: crinoidea)

The fine structure of all the constituent cell type of the crinoid axial organ is described (coelomic epithelial cells, muscles, free cells, gland cells and neurons) ; also described is the fine structure of the extracellular haemal fluid. The gland cells of the glandular tubules of the axial organ have the characteristic fine structure of protein exporting cells and may produce granular and filamentous components of the haemal fluid. The neurons (perikarya and axons) of the axial organ may possibly be neurosecretory, since they are filled with electron-dense granules. Homologies between the axial organs of different echinoderm classes are discussed.     

Fluid bilayer structure determination by the combined use of x-ray and neutron diffraction. II. "Composition-space" refinement method.

This is the second of two papers describing a method for the joint refinement of the structure of fluid bilayers using x-ray and neutron diffraction data. We showed in the first paper (Wiener, M. C., and S. H. White. 1990. Biophys. J. 59:162-173) that fluid bilayers generally consist of a nearly perfect lattice of thermally disordered unit cells and that the canonical resolution d/hmax is a measure of the widths of quasimolecular components represented by simple Gaussian functions. The thermal disorder makes possible a "composition space" representation in which the quasimolecular Gaussian distributions describe the number or probability of occupancy per unit length across the width of the bilayer of each component. This representation permits the joint refinement of neutron and x-ray lamellar diffraction data by means of a single quasimolecular structure that is fit simultaneously to both diffraction data sets. Scaling of each component by the appropriate neutron or x-ray scattering length maps the composition space profile to the appropriate scattering length space for comparison to experimental data. Other extensive properties, such as mass, can also be obtained by an appropriate scaling of the refined composition space structure. Based upon simple bilayer models involving crystal and liquid crystal structural information, we estimate that a fluid bilayer with hmax observed diffraction orders will be accurately represented by a structure with approximately hmax quasimolecular components. Strategies for assignment of quasimolecular components are demonstrated through detailed parsing of a phospholipid molecule based upon the one-dimensional projection of the crystal structure of dimyristoylphosphatidylcholine. Finally, we discuss in detail the number of experimental variables required for the composition space joint refinement. We find fluid bilayer structures to be marginally determined by the experimental data. The analysis of errors, which takes on particular importance under these circumstances, is also discussed.     

Transit time dispersion in the pulmonary arterial tree

Knowledge of the contributions of arterialand venous transit time dispersion to the pulmonary vascular transittime distribution is important for understanding lung function and forinterpreting various kinds of data containing information aboutpulmonary function. Thus, to determine the dispersion of blood transittimes occurring within the pulmonary arterial and venous trees, imagesof a bolus of contrast medium passing through the vasculature ofpump-perfused dog lung lobes were acquired by using an X-ray microfocalangiography system. Time-absorbance curves from the lobar artery andvein and from selected locations within the intrapulmonary arterial tree were measured from the images. Overall dispersion within the lunglobe was determined from the difference in the first and second moments(mean transit time and variance, respectively) of the inlet arterialand outlet venous time-absorbance curves. Moments at selected locationswithin the arterial tree were also calculated and compared with thoseof the lobar artery curve. Transit times for the arterial pathwaysupstream from the smallest measured arteries (200-µm diameter) wereless than ~20% of the total lung lobe mean transit time. Transittime variance among these arterial pathways (interpathway dispersion)was less than ~5% of the total variance imparted on the bolus as itpassed through the lung lobe. On average, the dispersion that occurredalong a given pathway (intrapathway dispersion) was negligible. Similar results were obtained for the venous tree. Taken together, the resultssuggest that most of the variation in transit time in theintrapulmonary vasculature occurs within the pulmonary capillary bedrather than in conducting arteries or veins.

     

Transventricular and transpial absorption of cerebrospinal fluid into cerebral microvessels

It is generally accepted that volume of cerebrospinal fluid (CSF) is secreted in brain ventricles and flows to subarachnoid space to be absorbed into dural venous sinuses or/and into lymphatics via perineural sheats of cranial nerves. Since 99% of CSF volume is water, in experiments on cats 3H-water was slowly infused into lateral ventricle and found that it does not flow to subarachnoid space but that it is rapidly absorbed transventricularly into periventricular capillaries. When 3H-water was infused in cortical subarachnoid space, it was absorbed locally into cerebral capillaries via pia mater. On the contrary, when macromolecule 3H-inulin is applied in CSF it is very slowly eliminated in bloodstream, and, with time, is carried by systolic-diastolic pulsations and mixing of CSF bidirectionally along CSF system. Thus, CSF volume (water) is absorbed rapidly into adjacent cerebral capillaries while inulin is distributed bidirectionally due to its long residence time in CSF Previously, the macromolecules have been used to study CSF volume hydrodynamics and with this misconception of CSF physiology arose.