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.     

Effect of head-down tilt on brain water distribution

Vascular and tissue fluid dynamics in the microgravity of space environments is commonly simulated by head-down tilt (HDT). Previous reports have indicated that intracranial pressure and extracranial vascular pressures increase during acute HDT and may cause cerebral edema. Tissue water changes within the cranium are detectable by T2 magnetic resonance imaging. We obtained T2 images of sagittal slices from five subjects while they were supine and during -13 degrees HDT using a 1.5-Tesla whole-body magnet. The analysis of difference images demonstrated that HDT leads to a 21% reduction of T2 in the subarachnoid cerebrospinal fluid (CSF) compartment and a 11% reduction in the eyes, which implies a reduction of water content; no increase in T2 was observed in other brain regions that have been associated with cerebral edema. These findings suggest that water leaves the CSF and ocular compartments by exudation as a result of increased transmural pressure causing water to leave the cranium via the spinal CSF compartment or the venous circulation.     

Osmotically absorbed water preferentially enters the cutaneous capillaries of the pelvic patch in the toad Bufo marinus

Cutaneously absorbed water in anurans has two potential routes of movement from the skin interstitium into the body fluids, via the cutaneous capillaries and/or the lymphatic system. We investigated the lymphatic route at the pelvic patch skin under the influence of isoproterenol and arginine vasotocin in Bufo marinus by continuously aspirating lymph from the lymph sacs draining the pelvic patch while the animals absorbed water. Changes in body mass, lymph mass, and lymph osmolality were measured. If absorbed water entered the lymph space directly, we expected, relative to controls, (1) no difference in change in body mass, (2) lymph mass to be greater, and (3) lymph osmolality to be lower. None of these predictions were confirmed. We also tested the possibility that absorbed water was stored in the skin interstitium by measuring the surface density of pelvic skin immediately after it absorbed water. If water was stored, we expected the surface density of this skin to be greater than that of control skin. No difference in surface density was found. These results provide strong evidence that absorbed water does not directly enter the lymphatic system and is not stored in the skin. Consequently, osmotically absorbed water must enter via a transcapillary route.     

In vitro study of cerebrospinal fluid dynamics in a shaken Basal cistern after experimental subarachnoid hemorrhage

Background

Cerebral arterial vasospasm leads to delayed cerebral ischemia and constitutes the major delayed complication following aneurysmal subarachnoid hemorrhage. Cerebral vasospasm can be reduced by increased blood clearance from the subarachnoid space. Clinical pilot studies allow the hypothesis that the clearance of subarachnoid blood is facilitated by means of head shaking. A major obstacle for meaningful clinical studies is the lack of data on appropriate parameters of head shaking. Our in vitro study aims to provide these essential parameters.

Methodology/Principal Findings

A model of the basal cerebral cistern was derived from human magnetic resonance imaging data. Subarachnoid hemorrhage was simulated by addition of dyed experimental blood to transparent experimental cerebrospinal fluid (CSF) filling the model of the basal cerebral cistern. Effects of various head positions and head motion settings (shaking angle amplitudes and shaking frequencies) on blood clearance were investigated using the quantitative dye washout method. Blood washout can be divided into two phases: Blood/CSF mixing and clearance. The major effect of shaking consists in better mixing of blood and CSF thereby increasing clearance rate. Without shaking, blood/CSF mixing and blood clearance in the basal cerebral cistern are hampered by differences in density and viscosity of blood and CSF. Blood clearance increases with decreased shaking frequency and with increased shaking angle amplitude. Head shaking facilitates clearance by varying the direction of gravitational force.

Conclusions/Significance

From this in vitro study can be inferred that patient or head shaking with large shaking angles at low frequency is a promising therapeutic strategy to increase blood clearance from the subarachnoid space.     

Uptake of peroxidase from the third ventricle by ependymal cells of the median eminence

Summary Peroxidase injected into the subarachnoid space in mice is absorbed by ependymal cells of the median eminence. The ependymal cells of the median eminence of the rat and Japanese quail absorb peroxidase injected into the third ventricle. The processes of these ependymal cells terminate at the capillaries of the primary plexus or those surrounding the ventromedial nucleus of the hypothalamus. In all three species, peroxidase is absorbed by the ependymal cells of the paraventricular organ and by those in close proximity to it. Some ependymal cells send processes to the capillaries in the lateral nucleus of the hypothalamus. These phenomena are discussed in relation to adenohypophysial function.A part of this investigation was effected while the senior author held a Visiting Professorship at the University of Giessen [Department of Anatomy (Professor A. Oksche, Director)].     

Recombinant canine distemper virus strain Snyder Hill expressing green or red fluorescent proteins causes meningoencephalitis in the ferret

The propensity of canine distemper virus (CDV) to spread to the central nervous system is one of the primary features of distemper. Therefore, we developed a reverse genetics system based on the neurovirulent Snyder Hill (SH) strain of CDV (CDV(SH)) and show that this virus rapidly circumvents the blood-brain and blood-cerebrospinal fluid (CSF) barriers to spread into the subarachnoid space to induce dramatic viral meningoencephalitis. The use of recombinant CDV(SH) (rCDV(SH)) expressing enhanced green fluorescent protein (EGFP) or red fluorescent protein (dTomato) facilitated the sensitive pathological assessment of routes of virus spread in vivo. Infection of ferrets with these viruses led to the full spectrum of clinical signs typically associated with distemper in dogs during a rapid, fatal disease course of approximately 2 weeks. Comparison with the ferret-adapted CDV(5804P) and the prototypic wild-type CDV(R252) showed that hematogenous infection of the choroid plexus is not a significant route of virus spread into the CSF. Instead, viral spread into the subarachnoid space in rCDV(SH)-infected animals was triggered by infection of vascular endothelial cells and the hematogenous spread of virus-infected leukocytes from meningeal blood vessels into the subarachnoid space. This resulted in widespread infection of cells of the pia and arachnoid mater of the leptomeninges over large areas of the cerebral hemispheres. The ability to sensitively assess the in vivo spread of a neurovirulent strain of CDV provides a novel model system to study the mechanisms of virus spread into the CSF and the pathogenesis of acute viral meningitis.     

Intercellular channels in the pars tuberalis of the rat hypophysis and their relationship to the subarachnoid space

Summary A system of intercellular channels is described in the pars tuberalis (PT) of the female rat. These spaces are lined by all types of cells found in the PT and are not sealed off by tight junctions. Ventrally and dorsally, the intercellular spaces open toward the basement membranes separating the PT from (i) the subarachnoid space, and (ii) the perivascular space of the portal capillaries, respectively. These intercellular channels differ from the follicles, which are also found in the PT, being lined by a particular type of cell.In a second group of female rats an epoxy mixture was injected into the third ventricle; 10 min thereafter horseradish peroxidase was infused into the cisterna magna. After processing the brain for the demonstration of exogenous peroxidase, it was found that the tracer had reached the subarachnoid space adjacent to the hypothalamus and entered into all ventricular cavities with the exception of the infundibular recess. Under these experimental conditions it was found that the tracer fills all intercellular channels of the PT, thus indicating that there is no barrier between the subarachnoid space and the PT. It is suggested that the subarachnoid space should be regarded as a probable route for the transport of trophic factor(s) and/or secretory product(s) of the PT.Supported by Grant S-80-13 from Directión de Investigaciones, Universidad Austral de Chile     

Cerebrospinal fluid flow and iodide131 transport in the spinal subarachnoid space

Free Na¹³¹ I and ¹³¹I-Albumin were injected in the cisterna magna of rhesus monkeys. The dynamics of descent into the spinal subarachnoid space and transport out of the cerebrospinal fluid were determined by gamma scintigraphy. ¹³¹I-Albumin moved slowly caudally, reaching the sacral CSF in three hours. Free Na¹³¹I was rapidly absorbed locally and did not descend. When its transport out of cerebrospinal fluid was inhibited by the addition of unlabeled isotonic Na I, ¹³¹I descended slowly at a rate parallel to that of tagged albumin. Injection of Na¹³¹I in hypertonic solutions caused immediate descent. Two minute periods of tumbling activity caused rapid movement of Na¹³¹I and ¹³¹I-Albumin into the lumbar spinal fluid. Na¹³¹I dynamics may serve as a model for other molecules actively transported out of cerebrospinal fluid, such as 5-hydroxy-indoleacetic acid; descent into caudal spinal fluid may depend on the degree of efflux from cerebrospinal fluid and on the animal's activity.     

Acidosis, Acetazolamide, and Amiloride: Effects on 22Na Transfer Across the Blood-Brain and Blood-CSF Barriers

Sprague-Dawley rats were given treatments, known to decrease 22Na movement into choroid plexus and CSF, to investigate their effect on 22Na transfer across the cerebral capillaries. Acidic salts, acetazolamide, or amiloride was injected intraperitoneally into bilaterally nephrectomized rats, and the rate of 22Na uptake into parietal cortex, pons-medulla, and CSF was determined at 12, 18, and 24 min. Severe acidosis (arterial pH 7.2), produced by HCl injection, decreased the rate of 22Na entry into both brain regions and CSF by 25%, whereas mild acidosis (pH 7.3) from NH4Cl injection reduced brain entry by 18%, but CSF entry by only 10%. Like HCl acidosis, amiloride reduced transport into both brain and CSF by 22%. Penetration of 22Na into parietal cortex was unchanged by acetazolamide, but that into CSF was slowed 30%. Since uptake of 22Na into cortical regions is primarily movement of tracer across the cerebral capillaries when tracer uptake time is less than 30 min, the results indicate that both metabolic acidosis and amiloride decrease Na+ permeativity at the cerebral capillaries as well as at the choroid plexus. Acetazolamide, on the other hand, alters Na+ movement only across the choroidal epithelium.     

Intracranial pressure accommodation is impaired by blocking pathways leading to extracranial lymphatics

Tracer studies indicate that cerebrospinal fluid (CSF) transport can occur through the cribriform plate into the nasal submucosa, where it is absorbed by cervical lymphatics. We tested the hypothesis that sealing the cribriform plate extracranially would impair the ability of the CSF pressure-regulating systems to compensate for volume infusions. Sheep were challenged with constant flow or constant pressure infusions of artificial CSF into the CSF compartment before and after the nasal mucosal side of the cribriform plate was sealed. With both infusion protocols, the intracranial pressure (ICP) vs. flow rate relationships were shifted significantly to the left when the cribriform plate was blocked. This indicated that obstruction of the cribriform plate reduced CSF clearance. Sham surgical procedures had no significant effects. Estimates of the proportional flow through cribriform and noncribriform routes suggested that cranial CSF absorption occurred primarily through the cribriform plate at low ICPs. Additional drainage sites (arachnoid villi or other lymphatic pathways) appeared to be recruited only when intracranial pressures were elevated. These data challenge the conventional view that CSF is absorbed principally via arachnoid villi and provide further support for the existence of several anatomically distinct cranial CSF transport pathways.     

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.     

Lymphatic Clearance of the Brain: Perivascular,Paravascular and Significance for Neurodegenerative Diseases

The lymphatic clearance pathways of the brain are different compared to the other organs of the body and have been the subject of heated debates. Drainage of brain extracellular fluids, particularly interstitial fluid (ISF) and cerebrospinal fluid (CSF), is not only important for volume regulation, but also for removal of waste products such as amyloid beta (Aβ). CSF plays a special role in clinical medicine, as it is available for analysis of biomarkers for Alzheimer’s disease. Despite the lack of a complete anatomical and physiological picture of the communications between the subarachnoid space (SAS) and the brain parenchyma, it is often assumed that Aβ is cleared from the cerebral ISF into the CSF. Recent work suggests that clearance of the brain mainly occurs during sleep, with a specific role for peri- and para-vascular spaces as drainage pathways from the brain parenchyma. However, the direction of flow, the anatomical structures involved and the driving forces remain elusive, with partially conflicting data in literature. The presence of Aβ in the glia limitans in Alzheimer’s disease suggests a direct communication of ISF with CSF. Nonetheless, there is also the well-described pathology of cerebral amyloid angiopathy associated with the failure of perivascular drainage of Aβ. Herein, we review the role of the vasculature and the impact of vascular pathology on the peri- and para-vascular clearance pathways of the brain. The different views on the possible routes for ISF drainage of the brain are discussed in the context of pathological significance.     

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.     

Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology

This review surveys evidence for the flow of brain interstitial fluid (ISF) via preferential pathways through the brain, and its relation to cerebrospinal fluid (CSF). Studies over >100 years have raised several controversial points, not all of them resolved. Recent studies have usefully combined a histological and a mathematical approach. Taken together the evidence indicates an ISF bulk flow rate of 0.1-0.3 microl min(-1) g(-1) in rat brain along preferential pathways especially perivascular spaces and axon tracts. The main source of this fluid is likely to be the brain capillary endothelium, which has the necessary ion transporters, channels and water permeability to generate fluid at a low rate, c1/100th of the rate per square centimeter of CSF secretion across choroid plexus epithelium. There is also evidence that a proportion of CSF may recycle from the subarachnoid space into arterial perivascular spaces on the ventral surface of the brain, and join the circulating ISF, draining back via venous perivascular spaces and axon tracts into CSF compartments, and out both through arachnoid granulations and along cranial nerves to the lymphatics of the neck. The bulk flow of ISF has implications for non-synaptic cell:cell communication (volume transmission); for drug delivery, distribution, and clearance; for brain ionic homeostasis and its disturbance in brain edema; for the immune function of the brain; for the clearance of beta-amyloid deposits; and for the migration of cells (malignant cells, stem cells).     

Niacinamide transport through the blood-brain barrier

The unidirectional influx of niacinamide across cerebral capillaries, the anatomical locus of the blood-brain barrier, was measured with an in situ rat brain perfusion technique employing [¹⁴C]niacinamide. Niacinamide was transported rapidly across the blood-brain barrier by a system that was not saturable with 10 mM niacinamide in the perfusate. However, with periods of perfusion longer than 30 seconds, there was substantial backflow of [¹⁴C]niacinamide into the perfusate. Niacinamide (1.7 M) transport through the blood-brain barrier was not significantly inhibited by 3-acetylpyridine. Thus, niacinamide is transported rapidly and bidirectionally through the blood-brain barrier by a high capacity transport system. Although involved in the transfer of niacinamide between blood and brain, this transport system does not play an important regulatory role in the synthesis of NMN, NAD, and NADP from niacinamide in brain.     

Metallomics study in CSF for putative biomarkers to predict cerebral vasospasm

Cerebral vasospasm (CV) refers to physical narrowing of brain cerebral arteries due to over-contraction of the arterial wall, which often arises following a subarachnoid hemorrhage (SAH). CV is frequently associated with poorer outcomes in those patients. Between the ictus of SAH and its CV complication, there is a 3-7 days delay, which provides a time window to predict and possibly prevent the onset CV. Since the precise pathomechanism of CV is still unclear and approaches for predicting it are inefficient, more effective ways of predicting CV need to be developed. As a protective nourishing fluid flows through the subarachnoid space, cerebrospinal fluid (CSF) closely relates to the health states of the central nervous system (CNS). Analysis of CSF can provide invaluable information to diagnose, treat and prevent diseases of the CNS because of its relatively direct representation of events in the brain. Therefore, we assume that the components in CSF and their alterations may reflect the state of aneurismal SAH and the development of vasospasm. In this study, three types of CSF from healthy control, and patients who suffered SAH and its complication, CV, were investigated via two-dimensional separations in combination with elemental and molecular mass spectrometry detection for the identification of elemental species. Size exclusion chromatography (SEC) was initially used with selective metal detection by inductively coupled plasma mass spectrometry (ICPMS) for characterizing size distribution of metal species. Various molecular distribution patterns were exhibited at different metal detection points (Fe, Ni, Cu, Zn and Pb). Further identification of possible metallopeptides and metalloprotein in tryptic digested fractions from the three sample types were made via reverse phase (RP)-Chip and electrospray mass spectrometry (MS) in combination with the Spectrum Mill data base search engine accessing appropriate data bases. Comparisons were generated to show suggested protein similarities or differences across the three CSF sample types. Six protein families with possible protein markers were further identified, and may be considered as possible focus areas for discovering valuable biomarkers to preclude the debilitating or deadly vasospasm.     

CSF distribution of morphine, methadone and sucrose after intrathecal injection

The lumbar to cisternal CSF distribution of morphine and methadone were compared to C-14 sucrose, a standard marker of CSF bulk flow, after lumbar subarachnoid injections in a sheep preparation. Morphine appeared and peaked simultaneously with C-14 sucrose in cisternal CSF at 90 to 190 minutes. The mean peak cisternal CSF morphine concentrations were sustained for 30-40 minutes, and averaged 148 ng/ml, representing 0.3% of the administered dose. Methadone was not detectable in cisternal CSF up to 240-300 minutes after lumbar subarachnoid administration. The C-14 sucrose/morphine ratio was increased an average of 6.7 times in cisternal CSF as compared to the ratio of the two compounds injected into the lumbar subarachnoid space. These studies demonstrate that morphine, a hydrophilic opioid, given intrathecally moves rostrally and appears in cisternal CSF by bulk flow. Furthermore the rostral redistribution of morphine is associated with the clearance of morphine from CSF. Methadone, a lipophilic opioid, appears to be completely cleared from CSF before it reaches the cisterna magna. These pharmacokinetic studies support a contribution of supraspinal sites to the analgesic and adverse effects produced by morphine given by spinal routes of administration. In contrast methadone appears to exert its effects predominantly at spinal sites.     

Antioxidant Therapy Against Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage

1. Approximately one-third of the morbidity and mortality due to aneurysmal subarachnoid hemorrhage (SAH) is caused by delayed ischemic neurological deficit (DIND) due to cerebral vasospasm.2. Compared to prolonged arterial constriction in other parts of the body, cerebral vasospasm is characterized by its long duration and refractoriness to vasodilators such as calcium antagonists.3. Whereas oxyhemoglobin (oxyHb) liberated into the CSF from the subarachnoid clot has been deemed the causative agent of vasoconstriction, the biochemical mechanisms whereby oxyHb elicits prolonged constriction of the cerebral arteries has remained elusive. Here, we suggest that oxyHb triggers the generation of reactive oxygen intermediates (ROI) within the CSF.4. Multiple lines of evidence indicate that the occurrence of vasospasm, namely, prolonged smooth muscle contraction, is due to the following intracellular events.5. First, hydroxyl radicals (OH*), the most reactive species of ROI, are generated within the cerebral arterial wall via the Fenton and Haber–Weiss reactions catalyzed by oxyHb. Second, subsequent peroxidative membrane damage in the arterial smooth muscle cell enhances the metabolism of phosphatidylcholine and phosphatidylethanolamine, leading to a rise in the intracellular level of diacylglycerol, an endogenous activator of protein kinase C.6. The prolonged arterial contraction that occurs during vasospasm is attributable primarily to the activation of protein kinase C, not to the Ca²⁺/calmodulin system. In this article, literature relevant to the above thesis is reviewed, and the rationale for the antioxidant therapy against cerebral vasospasm is discussed.     

VITAMIN B6 TRANSPORT IN THE CENTRAL NERVOUS SYSTEM: IN VIVO STUDIES

Abstract— The total concentrations of vitamin B₆ (B₆) in plasma, choroid plexus, CSF and brain of adult New Zealand white rabbits, measured fluorometrically, were 0.30, 15.10, 0.39 and 8.90 μ mol/l or kg respectively. The mechanisms by which B₆ enters and leaves brain, choroid plexus and CSF were investigated by injecting [³H]pyridoxine (PIN) intravenously, intraventricularly and intraarterially. [³H]PIN, with or without unlabelled PIN, was infused intravenously at a constant rate into conscious rabbits. At 150 min, [³H]B₆ readily entered CSF, choroid plexus and brain. The addition of 0.5 mmol/kg carrier PIN to the infusion solution depressed the relative entry of [³H]B₆ into CSF, choroid plexus and brain by about 80%. After intraventricular injection, [³H]PIN readily entered brain from CSF. The intraventricular injection of carrier PIN with [³H]PIN decreased the amount of [³H]B₆ in brain and also decreased the percentage of [³H]B₆ in CSF and brain that was phosphorylated. During one pass through the cerebral circulation, [³H]PIN (1 μ m ) was cleared from the circulation no more rapidly than mannitol. These results were interpreted as showing that the entry of B₆ from blood into CSF and presumably the extracellular space of brain and thence into brain cells involves one or more saturable transport and/or metabolic steps.     

Modélisation des flux cérébraux par une analogie électrique : validation par vélocimétrie IRM

The cine Phase-Contrast Magnetic Resonance (PCMR) sequence is the only noninvasive technique for the study of cerebrospinal fluid (CSF) oscillations. It can provide CSF and blood flow measurements throughout the cardiac cycle. To study cerebral hydro-hemodynamic, models have been developed; nevertheless the majority of these models did not take into account the CSF oscillations. The objective of this study was to establish reference values for cerebral hydro-hemodynamic and propose a new electrical model of the brain dynamics.Material and methodsCSF and blood flows were measured in 19 control subjects by PCMR imaging. Dynamic flow images were analyzed on dedicated software to reconstruct the flow curves during the cardiac cycle. An electrical analogue was realized. The inputs of the model were fed by PCMR arterial and venous flows to simulate CSF oscillations. The simulated CSF oscillations were compared to the measured CSF oscillations to validate the model.ResultsThe key parameters of the CSF and blood flow curves were obtained, e.g. total cerebral blood flow was 688 ± 115 mL/min, ventricular CSF oscillatory volume was 0.05 ± 0.02 mL/cardiac cycle, and the subarachnoid CSF oscillatory volume was 0.55 ± 0.15 mL/cardiac cycle. A close agreement was found between measured and simulated cerebral CSF oscillations.ConclusionThis study established the main values characterizing cerebral hydrodynamics in a control population. It provided a better understanding of the mechanisms of intracranial volumes regulation during the cardiac cycle. Our results are now used in clinical practice and the model proposed is effective to study cerebral hydro-hemodynamic.