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.     

The pathogenesis of normal pressure hydrocephalus: A theoretical analysis

Hydrocephalus is an abnormal accumulation of cerebrospinal fluid (CSF) in the cerebral ventricles, usually caused by impaired absorption of the fluid into the bloodstream. Despite obstructed absorption and continued secretion of CSF into the ventricles at a near normal rate, the ventricular CSF pressure (VCSFP) is often normal. We attempt to understand how hydrocephalus can exist with normal VCSFP by exploring the role of the brain parenchyma in absorbing CSF in hydrocephalus. We test three theories: (1) the ventricular wall is impermeable to CSF; (2) ventricular CSF seeps into the parenchyma, from which it is efficiently absorbed; and (3) ventricular CSF seeps into the parenchyma but is absorbed inefficiently. We model the brain as a thick spherical shell consisting of a porous, elastic, solid matrix, containing interstitial fluid and blood. We modify the equations of poroelasticity, which describe flow of fluid through porous solids, to allow for parenchymal absorption. For each of the three theories we calculate the steady state changes in VCSFP and in parenchymal fluid pressure caused by an incremental defect in CSF absorption. We also calculate the steady state changes in fluid content, tissue volume, tissue displacement, and stresses caused by a small increment of VCSFP. We conclude that only the second theory—seepage of CSF with efficient parenchymal absorption—accounts for the clinical features of normal pressure hydrocephalus. These features include sustained ventricular dilatation despite normal VCSFP, increased periventricular fluid content, and localized periventricular white matter damage.     

Models of the pulsatile hydrodynamics of cerebrospinal fluid flow in the normal and abnormal intracranial system

Images obtained from magnetic resonance imaging have helped to ascertain that both the cerebrospinal fluid (CSF) and brain move in a pulsatile manner within the cranium. However, these images are not able to reveal any quantitative information on the physiological forces that are associated with pulsatile motion. Understanding both the pressure and velocity flow field of CSF in the ventricles is important to help understand the mechanics of hydrocephalus. Four separate fluid structure interaction models of the ventricular system in the sagittal plane were created for this purpose. The first model was of a normal brain. The second and third models were pathological brain models with aqueductal stenosis at various locations along the fluid pathway. The fourth model was of a hydrocephalic brain. Results revealed the hydrodynamics of CSF pulsatile flow in the ventricles of these models. Most importantly, it has also revealed the different changes in CSF pulsatile hydrodynamics caused by the various locations of fluid flow obstructions.     

Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus

Cilia are complex organelles involved in sensory perception and fluid or cell movement. They are constructed through a highly conserved process called intraflagellar transport (IFT). Mutations in IFT genes, such as Tg737, result in severe developmental defects and disease. In the case of the Tg737orpk mutants, these pathological alterations include cystic kidney disease, biliary and pancreatic duct abnormalities, skeletal patterning defects, and hydrocephalus. Here, we explore the connection between cilia dysfunction and the development of hydrocephalus by using the Tg737orpk mutants. Our analysis indicates that cilia on cells of the brain ventricles of Tg737orpk mutant mice are severely malformed. On the ependymal cells, these defects lead to disorganized beating and impaired cerebrospinal fluid (CSF) movement. However, the loss of the cilia beat and CSF flow is not the initiating factor, as the pathology is present prior to the development of motile cilia on these cells and CSF flow is not impaired at early stages of the disease. Rather, our results suggest that loss of cilia leads to altered function of the choroid plexus epithelium, as evidenced by elevated intracellular cAMP levels and increased chloride concentration in the CSF. These data suggest that cilia function is necessary for regulating ion transport and CSF production, as well as for CSF flow through the ventricles.     

Totally tubular: the mystery behind function and origin of the brain ventricular system

A unique feature of the vertebrate brain is the ventricular system, a series of connected cavities which are filled with cerebrospinal fluid (CSF) and surrounded by neuroepithelium. While CSF is critical for both adult brain function and embryonic brain development, neither development nor function of the brain ventricular system is fully understood. In this review, we discuss the mystery of why vertebrate brains have ventricles, and whence they originate. The brain ventricular system develops from the lumen of the neural tube, as the neuroepithelium undergoes morphogenesis. The molecular mechanisms underlying this ontogeny are described. We discuss possible functions of both adult and embryonic brain ventricles, as well as major brain defects that are associated with CSF and brain ventricular abnormalities. We conclude that vertebrates have taken advantage of their neural tube to form the essential brain ventricular system.     

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.     

Comparison of the Relationship between Cerebral White Matter and Grey Matter in Normal Dogs and Dogs with Lateral Ventricular Enlargement

Large cerebral ventricles are a frequent finding in brains of dogs with brachycephalic skull conformation, in comparison with mesaticephalic dogs. It remains unclear whether oversized ventricles represent a normal variant or a pathological condition in brachycephalic dogs. There is a distinct relationship between white matter and grey matter in the cerebrum of all eutherian mammals. The aim of this study was to determine if this physiological proportion between white matter and grey matter of the forebrain still exists in brachycephalic dogs with oversized ventricles. The relative cerebral grey matter, white matter and cerebrospinal fluid volume in dogs were determined based on magnetic-resonance-imaging datasets using graphical software. In an analysis of covariance (ANCOVA) using body mass as the covariate, the adjusted means of the brain tissue volumes of two groups of dogs were compared. Group 1 included 37 mesaticephalic dogs of different sizes with no apparent changes in brain morphology, and subjectively normal ventricle size. Group 2 included 35 brachycephalic dogs in which subjectively enlarged cerebral ventricles were noted as an incidental finding in their magnetic-resonance-imaging examination. Whereas no significant different adjusted means of the grey matter could be determined, the group of brachycephalic dogs had significantly larger adjusted means of lateral cerebral ventricles and significantly less adjusted means of relative white matter volume. This indicates that brachycephalic dogs with subjective ventriculomegaly have less white matter, as expected based on their body weight and cerebral volume. Our study suggests that ventriculomegaly in brachycephalic dogs is not a normal variant of ventricular volume. Based on the changes in the relative proportion of WM and CSF volume, and the unchanged GM proportions in dogs with ventriculomegaly, we rather suggest that distension of the lateral ventricles might be the underlying cause of pressure related periventricular loss of white matter tissue, as occurs in internal hydrocephalus.     

脑出血后脑积水形成机制研究进展

脑积水是由于颅脑疾患使得脑脊液分泌过多或(和)循环、吸收障碍而致颅内脑脊液量增加,脑室系统扩大或(和)蛛网膜下腔扩大的一种病症。目前多项临床多因素回归分析及前瞻性随机对照研究已证实脑积水是脑出血(intracerebral hemorrhage,ICH)预后不良的独立危险因素。脑积水以脑萎缩及神经功能障碍为主要特征,严重影响人的认知功能和生活质量,给患者家庭及社会带来巨大的经济负担。本人就ICH后脑积水形成机制研究进展做一综述。     

A clinical,pneumoencephalographic and radioisotopic study of normal-pressure communicating hydrocephalus

Human serum albumin labelled with iodine-133 or technetium-99^m was injected by the lumbar or cisternal route into patients suspected of having communicating hydrocephalus, and scintigrams were performed up to 24 hours after injection.The CSF isotope studies were shown to be a valuable adjunct to clinical examination and pneumoencephalography in the diagnosis of hydrocephalus. This was especially true in suspected cases of “normal”-pressure hydrocephalus where there may be considerable uncertainty as to which patients with normal pressure and enlarged ventricles will benefit from a shunting procedure. The CSF isotope study provides useful information to the clinician in differentiating patients with symptomatic hydrocephalus from the larger group with dementia, cerebral atrophy and hydrocephalus ex vacuo.     

Transependymal Cerebrospinal Fluid Flow: Opportunity for Drug Delivery?

Drug delivery to the central nervous system (CNS) is complicated by the blood-brain barrier. As a result, many agents that are found to be potentially effective at their site of action cannot be sufficiently or effectively delivered to the CNS and therefore have been discarded and not developed further for clinical use, leaving many CNS diseases untreated. One way to overcome this obstacle is intracerebroventricular (ICV) delivery of the therapeutics directly to cerebrospinal fluid (CSF). Recent experimental and clinical findings reveal that CSF flows from the ventricles throughout the parenchyma towards the subarachnoid space also named minor CSF pathway, while earlier, it was suggested that only in pathological conditions such as hydrocephalus this form of CSF flow occurs. This transependymal flow of CSF provides a route to distribute ICV-infused drugs throughout the brain. More insight on transependymal CSF flow will direct more rational to ICV drug delivery and broaden its clinical indications in managing CNS diseases.     

Ventricle equilibrium position in healthy and normal pressure hydrocephalus brains using an analytical model

The driving force that causes enlargement of the ventricles remains unclear in case of normal pressure hydrocephalus (NPH). Both healthy and NPH brain conditions are characterized by a low transparenchymal pressure drop, typically 1 mm Hg. The present paper proposes an analytical model for normal and NPH brains using Darcy's and Biot's equations and simplifying the brain geometry to a hollow sphere with an internal and external radius. Self-consistent solutions for the large deformation problem that is associated with large ventricle dilation are presented and the notion of equilibrium or stable ventricle position is highlighted for both healthy and NPH conditions. The influence of different biomechanical parameters on the stable ventricle geometry is assessed and it is shown that both CSF seepage through the ependyma and parenchymal permeability play a key role. Although very simple, the present model is able to predict the onset and development of NPH conditions as a deviation from healthy conditions.     

High-pressure hydrocephalus: a novel analytical modeling approach

Hydrocephalus is an abnormal accumulation of cerebrospinal fluid (CSF) within ventricles and subarachnoid space (SAS) as a result of disturbances in secretion or absorption procedures. It is believed that arachnoid villi cells, which are microscopic projections of pia-arachnoid mater that extend into venous channels in sagittal sinus, are the main sites for CSF absorption, but it is tempting to speculate that a significant portion of CSF is removed from the SAS by nasal lymphatic vessels around olfactory nerve. Thus, in this paper, we propose an analytical model of CSF-lymphatic-blood circulation, in which these two output pathways for CSF absorption have been considered. Mathematical relations governing the pressures in different interacting compartments of the brain are considered. In addition, for increasing the similarity of our model to the physiological conditions, the bulk flow mechanism, which is supposed to occur during CSF absorption, has been considered in our model. We used our model to simulate hydrocephalus. The results indicate that the lymphatic disorders have more considerable effect in decreasing CSF absorption, compared to the disturbances in arachnoid villi cells. Based on our modeling, we believe that disorders in lymphatic pathway may be a cause of high-pressure hydrocephalus. Surely experimental studies are required to validate our hypothesis.     

Investigating structural brain changes of dehydration using voxel-based morphometry

Dehydration can affect the volume of brain structures, which might imply a confound in volumetric and morphometric studies of normal or diseased brain. Six young, healthy volunteers were repeatedly investigated using three-dimensional T(1)-weighted magnetic resonance imaging during states of normal hydration, hyperhydration, and dehydration to assess volume changes in gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). The datasets were analyzed using voxel-based morphometry (VBM), a widely used voxel-wise statistical analysis tool, FreeSurfer, a fully automated volumetric segmentation measure, and SIENAr a longitudinal brain-change detection algorithm. A significant decrease of GM and WM volume associated with dehydration was found in various brain regions, most prominently, in temporal and sub-gyral parietal areas, in the left inferior orbito-frontal region, and in the extra-nuclear region. Moreover, we found consistent increases in CSF, that is, an expansion of the ventricular system affecting both lateral ventricles, the third, and the fourth ventricle. Similar degrees of shrinkage in WM volume and increase of the ventricular system have been reported in studies of mild cognitive impairment or Alzheime [Formula: see text]s disease during disease progression. Based on these findings, a potential confound in GM and WM or ventricular volume studies due to the subjects' hydration state cannot be excluded and should be appropriately addressed in morphometric studies of the brain.     

Junctional Adhesion Molecule (JAM)-C Deficient C57BL/6 Mice Develop a Severe Hydrocephalus

The junctional adhesion molecule (JAM)-C is a widely expressed adhesion molecule regulating cell adhesion, cell polarity and inflammation. JAM-C expression and function in the central nervous system (CNS) has been poorly characterized to date. Here we show that JAM-C^−/− mice backcrossed onto the C57BL/6 genetic background developed a severe hydrocephalus. An in depth immunohistochemical study revealed specific immunostaining for JAM-C in vascular endothelial cells in the CNS parenchyma, the meninges and in the choroid plexus of healthy C57BL/6 mice. Additional JAM-C immunostaining was detected on ependymal cells lining the ventricles and on choroid plexus epithelial cells. Despite the presence of hemorrhages in the brains of JAM-C^−/− mice, our study demonstrates that development of the hydrocephalus was not due to a vascular function of JAM-C as endothelial re-expression of JAM-C failed to rescue the hydrocephalus phenotype of JAM-C^−/− C57BL/6 mice. Evaluation of cerebrospinal fluid (CSF) circulation within the ventricular system of JAM-C^−/− mice excluded occlusion of the cerebral aqueduct as the cause of hydrocephalus development but showed the acquisition of a block or reduction of CSF drainage from the lateral to the 3^rd ventricle in JAM-C^−/− C57BL/6 mice. Taken together, our study suggests that JAM-C^−/− C57BL/6 mice model the important role for JAM-C in brain development and CSF homeostasis as recently observed in humans with a loss-of-function mutation in JAM-C.     

An Assay for Permeability of the Zebrafish Embryonic Neuroepithelium

The brain ventricular system is conserved among vertebrates and is composed of a series of interconnected cavities called brain ventricles, which form during the earliest stages of brain development and are maintained throughout the animal''s life. The brain ventricular system is found in vertebrates, and the ventricles develop after neural tube formation, when the central lumen fills with cerebrospinal fluid (CSF) ^1,2. CSF is a protein rich fluid that is essential for normal brain development and function^3-6.In zebrafish, brain ventricle inflation begins at approximately 18 hr post fertilization (hpf), after the neural tube is closed. Multiple processes are associated with brain ventricle formation, including formation of a neuroepithelium, tight junction formation that regulates permeability and CSF production. We showed that the Na,K-ATPase is required for brain ventricle inflation, impacting all these processes ^7,8, while claudin 5a is necessary for tight junction formation ⁹. Additionally, we showed that "relaxation" of the embryonic neuroepithelium, via inhibition of myosin, is associated with brain ventricle inflation.To investigate the regulation of permeability during zebrafish brain ventricle inflation, we developed a ventricular dye retention assay. This method uses brain ventricle injection in a living zebrafish embryo, a technique previously developed in our lab¹⁰, to fluorescently label the cerebrospinal fluid. Embryos are then imaged over time as the fluorescent dye moves through the brain ventricles and neuroepithelium. The distance the dye front moves away from the basal (non-luminal) side of the neuroepithelium over time is quantified and is a measure of neuroepithelial permeability (Figure 1). We observe that dyes 70 kDa and smaller will move through the neuroepithelium and can be detected outside the embryonic zebrafish brain at 24 hpf (Figure 2).This dye retention assay can be used to analyze neuroepithelial permeability in a variety of different genetic backgrounds, at different times during development, and after environmental perturbations. It may also be useful in examining pathological accumulation of CSF. Overall, this technique allows investigators to analyze the role and regulation of permeability during development and disease.     

Characterization of the human ventricular cerebrospinal fluid proteome obtained from hydrocephalic patients

The continuing expansion of proteomic technology has been fueled by the potential for discovering novel biomarkers that may be used for the early detection of disease. It has been proposed that human cerebrospinal fluid (CSF), which surrounds and protects the brain and spinal cord from traumatic injury, may be a valuable target for the diagnosis of a variety of conditions such as Alzheimer's disease, traumatic brain injury, amyotrophic lateral sclerosis and Parkinson's disease. The immense complexity of biofluids, however, still requires that considerable development be made in the analytical techniques used so that comprehensive coverage of the proteins present in such samples is achieved. Using a simple separation strategy the protein complement of human ventricular cerebrospinal fluid obtained from patients with hydrocephalus was evaluated. The study resulted in the identification of over 1500 unique proteins that were found within all nine CSF samples that were analyzed. Comparison with the HUPO serum proteome database demonstrated that human ventricular CSF contains a large array of proteins that may be unique to CSF. This analysis greatly increases our knowledge of the protein content of this clinically important biofluid.     

The system of cerebrospinal fluid-contacting neurons. Its supposed role in the nonsynaptic signal transmission of the brain

Recent investigations confirm the importance of nonsynaptic signal transmission in several functions of the nervous tissue. Present in various periventricular brain regions of vertebrates, the system of cerebrospinal fluid (CSF)-contacting neurons seems to have a special role in taking up, transforming and emitting nonsynaptic signals mediated by the internal and external CSF and intercellular fluid of the brain. Most of the CSF-contacting nerve cells send dendritic processes into the internal CSF of the brain ventricles or central canal where they form terminals bearing stereocilia and a 9+0-, or 9+2-type cilium. Some of these neurons resemble known sensory cells of chemoreceptor-type, others may be sensitive to the pressure or flow of the CSF, or to the illumination of the brain tissue. The axons of the CSF-contacting neurons transmit information taken up by dendrites and perikarya to synaptic zones of various brain areas. By forming neurohormonal terminals, axons also contact the external CSF space and release various bioactive substances there. Some perikarya send their axons into the internal CSF, and form free endings there, or synapses on intraventricular dendrites, perikarya and/or on the ventricular surface of ependymal cells. Contacting the intercellular space, sensory-type cilia were also demonstrated on nerve cells situated in the brain tissue subependymally or farther away from the ventricles. Among neuronal elements entering the internal CSF-space, the hypothalamic CSF-contacting neurons are present in the magnocellular and parvicellular nuclei and in some circumventricular organs like the paraventricular organ and the vascular sac. The CSF-contacting dendrites of all these areas bear a solitary 9 x 2+0-type cilium and resemble chemoreceptors cytologically. In electrophysiological experiments, the neurons of the paraventricular organ are highly sensitive to the composition of the ventricular CSF. The axons of the CSF-contacting neurons terminate not only in the hypothalamic synaptic zones but also in tel-, mes- and rhombencephalic nuclei and reach the spinal cord as well. The supposed chemical information taken up by the CSF-contacting neurons from the ventricular CSF may influence the function of these areas of the central nervous system. Some nerve cells of the photoreceptor areas form sensory terminals similar to those of the hypothalamic CSF-contacting neurons. Special secondary neurons of the retina and pineal organ contact the retinal photoreceptor space and pineal recess respectively, both cavities being embryologically derived from the 3rd ventricle. The composition of these photoreceptor spaces is important in the photochemical transduction and may modify the activity of the secondary neurons. Septal and preoptic CSF-contacting neurons contain various opsins and other compounds of the phototransduction cascade and represent deep encephalic photoreceptors detecting the illumination of the brain tissue and play a role in the regulation of circadian and reproductive responses to light. The medullo-spinal CSF-contacting neurons present in the oblongate medulla, spinal cord and terminal filum, send their dendrites into the fourth ventricle and central canal. Resembling mechanoreceptors of the lateral line organ, the spinal CSF-contacting neurons may be sensitive to the pressure or flow of the CSF. The axons of these neurons terminate at the external CSF-space of the oblongate medulla and spinal cord and form neurohormonal nerve endings. Based on information taken up from the CSF, a regulatory effect on the production or composition of CSF was supposed for bioactive materials released by these terminals. Most of the axons of the medullospinal CSF-contacting neurons and the magno- and parvicellular neurosecretory nuclei running to neurohemal areas (neurohypophysis, median eminence, terminal lamina, vascular sac and urophysis) do not terminate directly on vessels, instead they form neurohormonal nerve terminals attached by half-desmosomes on the basal lamina of the external and vascular surface of the brain tissue. Therefore, the bioactive materials released from these terminals primarily enter the external CSF and secondarily, by diffusion into vessels and the composition of the external CSF, may have a modulatory effect on the bioactive substances released by the neurohormonal terminals. Contacting the intercellular space, sensory-type cilia were also demonstrated on nerve cells situated subependymally or farther away from the ventricles, among others in the neurosecretory nuclei. Since tight-junctions are lacking between ependymal cells of the ventricular wall, not only CSF-contacting but also subependymal ciliated neurons may be influenced by the actual composition of the CSF besides that of the intercellular fluid of the brain tissue. According to the comparative histological data summarised in this review, the ventricular CSF-contacting neurons represent the phylogenetically oldest component detecting the internal fluid milieu of the brain. The neurohormonal terminals on the external surface of the brain equally represent an ancient form of nonsynaptic signal transmission.     

Craniofacial configuration and postcranial development of a hydrocephalic child (ca. 2500 B.C.-500 A.D.): with a review of cases and comment on diagnostic criteria

Hydrocephalus is a severe disorder of the central nervous system characterized by absorption blockage of the cerebral spinal fluid (CSF). The archaeological record of the condition ranges in time from 10,000 B.C. to 1670 A.D. and consists of 30 possible cases worldwide. A review of this material reveals that diagnostic criteria which fully delineate the condition have not been established. Previously, no attempt has been made to differentiate the two major categories of hydrocephalus and their subgroupings, or to identify other conditions which might result in similar morphologies. A partial child's skeleton from the Middle Period (ca. 2500 B.C. to 500 A.D.) of Central California Prehistory is described in light of an extensive clinical literature. Examination of this individual reveals a unique craniofacial configuration and malformed postcrania. Bony criteria for a differential diagnosis of hydrocephalus are established and applied to this individual. Based on these criteria, the individual is diagnosed as having a chronic form of noncommunicating hydrocephalus. Blockage of the CSF pathway most likely occurred in the aqueduct of Sylvius with a partial occlusion of the foramen of Monro or a frontal cyst. In addition, femoral development is suggestive of partial paralysis.     

Brain amine metabolism is reflected in cerebral ventricular CSF

The choroid plexuses are suspended within the ventricles and account for approximately 75% of CSF production. The sodium-potassium ATPase operates within the choroidal epithelial cells and moves sodium ions towards the ventricular surface and potassium ions in the direction of the stroma. Water flows into CSF along osmotic gradient produced by sodium pump. The existence of extracellular channels by which brain metabolites could passively diffuse into the ventriculosubarachnoid space suggests an excretory role for CSF. Removal of solutes from the CSF could occur across the choroidal epithelium or arachnoid membrane into the blood. Systematically administered monoamine metabolites do not cross the blood-brain or the blood-CSF barrier. The regional concentrations of amine metabolites in the CSF is in part a reflection of the concentration of catecholamines and indoleamines in the immediately adjacent neuronal parenchyma. In order to illustrate the validity of monoamine metabolite determinations in cerebral ventricular CSF we developed a device which allowed for a continuous third ventricular CSF withdrawal in freely moving (or anesthetized) rats at a constant flow of 1 microliter/min. The elevation of biogenic amine metabolites in CSF by probenecid or their decline by monoamine oxidase inhibition was used to assess the rate of turnover of amines. Pharmacological manipulations (yohimbine, haloperidol, ouabain) resulted in mono-amine metabolite fluctuations in CSF similar to those previously described in brain tissue. Insulin administration caused an abrupt decrease in CSF glucose and elevated dopamine and serotonin metabolites in rats which had no access to food. These studies demonstrate the adaptation of in vivo analysis of CSF in rats but also exemplify the usefulness of monoamine metabolite determination in the CSF as indicators of brain function.     

蛛网膜下腔出血合并脑积水的治疗方法探讨

目的:探讨蛛网膜下腔出血(SAH)合并脑积水的治疗方法。方法:回顾性分析31例SAH合并脑积水患者的临床资料,除常规脱水、防治血管痉挛、营养神经等治疗方法外,其中10例给予行脑室-腹腔分流术,21例行侧脑室外引流术,对比分析两种治疗方案的利弊。结果:10例脑室-腹腔分流术患者9例手术效果良好,术后复查颅脑CT显示脑室明显减小,间质水肿消失,1例患者术后1月内再次出现脑积水,给予行同侧分流管探查再通、对侧脑室-腹腔分流术,术后效果良好,颅脑CT示脑室减小。21例行侧脑室外引流术患者,术后感染2例,全部患者均术后7天内拔除引流管,术后1月9例复发脑积水,给予再次行脑室-腹腔分流术,术后效果良好。结论:在手术指征明确的情况下,早期给予SAH合并脑积水患者行脑室腹腔分流术,分流管堵塞可能性小,术后感染发生率低,临床效果令人满意。