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New experimental and clinical findings question the historic view of hydrocephalus and its 100-year-old classification. In particular, real-time magnetic resonance imaging (MRI) evaluation of cerebrospinal fluid (CSF) flow and detailed insights into brain water regulation on the molecular scale indicate the existence of at least three main mechanisms that determine the dynamics of neurofluids: (1) inspiration is a major driving force; (2) adequate filling of brain ventricles by balanced CSF upsurge is sensed by cilia; and (3) the perivascular glial network connects the ependymal surface to the pericapillary Virchow–Robin spaces. Hitherto, these aspects have not been considered a common physiologic framework, improving knowledge and therapy for severe disorders of normal-pressure and posthemorrhagic hydrocephalus, spontaneous intracranial hypotension, and spaceflight disease.

Brain ventricle is one of the biomarkers for detecting neurological disorders. Studying the shape of the ventricles will aid in the diagnosis process of atrophy and other CSF-related neurological disorders, as ventricles are filled with CSF. This paper introduces a spectral analysis algorithm based on wave kernel signature. This shape signature was used for studying the shape of segmented ventricles from the brain images. Based on the shape signature, the study groups were classified as normal subjects and atrophy subjects. The proposed algorithm is simple, effective, automated, and less time consuming. The proposed method performed better than the other methods heat kernel signature, scale invariant heat kernel signature, wave kernel signature, and spectral graph wavelet signature, which were used for validation purpose, by producing 94-95% classification accuracy by classifying normal and atrophy subjects correctly for CT, MR, and OASIS datasets.

Amyloid-β (Aβ) and tau oligomers have been identified as neurotoxic agents responsible for causing Alzheimer’s disease (AD). Clinical trials using Aβ and tau as targets have failed, giving rise to calls for new research approaches to combat AD. This paper provides such an approach. Most basic AD research has involved quiescent Aβ and tau solutions. However, studies involving laminar and extensional flow of proteins have demonstrated that mechanical agitation of proteins induces or accelerates protein aggregation. Recent MRI brain studies have revealed high energy, chaotic motion of cerebrospinal fluid (CSF) in lower brain and brainstem regions. These and studies showing CSF flow within the brain have shown that there are two energetic hot spots. These are within the third and fourth brain ventricles and in the neighborhood of the circle of Willis blood vessel region. These two regions are also the same locations as those of the earliest Aβ and tau AD pathology. In this paper, it is proposed that cardiac systolic pulse waves that emanate from the major brain arteries in the lower brain and brainstem regions and whose pulse waves drive CSF flows within the brain are responsible for initiating AD and possibly other amyloid diseases. It is further proposed that the triggering of these diseases comes about because of the strengthening of systolic pulses due to major artery hardening that generates intense CSF extensional flow stress. Such stress provides the activation energy needed to induce conformational changes of both Aβ and tau within the lower brain and brainstem region, producing unique neurotoxic oligomer molecule conformations that induce AD.

Background Although maternal MeHg-exposure causes hydrocephalus in the offspring of mice, its pathogenesis has not been fully explained. In the present study, we examined the issue of how maternal MeHg-exposure in mice affects ependymal ciliary movement in the offspring and whether the lateral ventricles in offspring show dilation. Methods Pregnant mice were given drinking water containing 0, 10, or 20 mg/L MeHg, or a single dose of 2 mg/kg MeHg. Brain slices were prepared from the offspring and the ependymal ciliary movement of ependymal cells in the third ventricle were observed by a high-speed digital camera. The dilation of the lateral ventricles in the offspring was assessed by histological examination. Results The administration of MeHg in the drinking water of pregnant mice at levels of 10 mg/L and 20 mg/L MeHg from GD10 to birth caused a significant decrease of ciliary beating frequency (CBF) in ependymal cells of the third ventricle in the weaned offspring. The ependymal ciliary movement of the weaned offspring was particularly sensitive in the case of the administration of MeHg at GD10. Moreover, there was a significant dilation of cross-sectional areas of lateral ventricles in weaned offspring from the pregnant mice that had been administered MeHg. The CBF and the cross-sectional areas of the lateral ventricles improved with time. Conclusions These results suggest that the impairment of ependymal ciliary movement by maternal MeHg-exposure contributes to the development of hydrocephalus in the offspring.

Although the central canal is an integral component of the cerebral ventricular system, central canal dilation has not been examined adequately during the progression of subarachnoid hemorrhage-related hydrocephalus (SAH-H). Central canal dilation-associated ependymal cell desquamation or subependymal membrane rupture has been rarely reported. Herein, we try to describe possible mechanisms of central canal dilation "Hydromyelia," developing after SAH. A total of 25 New Zealand hybrid female rabbits were recruited. Five served as controls, and five received sham operations. In the remaining animals (n = 15), 0.5 mL/kg of autologous blood was injected into the cisterna magna twice on 0 and 2nd days. Five of these animals died within a few days. A total of 10 survivor animals decapitated 3 weeks later, and the brains and cervical spinal cords were histologically examined. Central canal volumes, ependymal cell numbers on the canal surfaces, and the Evans' indices of the ventricles were compared. On histological examination, central canal occlusion with desquamated ependymal cells and basement membrane rupture were evident. The mean Evans' index of the brain ventricles was 0.31, the mean central canal volume was 1.054 mm3, and the normal ependymal cell density was 4.210/mm2 in control animals; the respective values were 0.34, 1.287 mm3, and 3.602/mm2 for sham-operated animals, and 0.41, 1.776 mm3, and 2.923/mm2 in the study group. The differences were statistically significant (p < 0.05). Hydromyelia, an ignored complication of SAH-H, features ependymal cell desquamation, subependymal basement membrane destruction, blood cell accumulation on the subependymal cell basement membrane, and increased CSF pressure. Hydromyelia may be a significant complication following SAH.

The mold of the human cerebral ventricles produced in 1918 by Walter E. Dandy had an experimental precedent, a wax cast of ox ventricles made four hundred years earlier (1508-9) by Leonardo da Vinci (1452-1519). This paper is an homage to the epitome of Renaissance and polymath Leonard da Vinci, as well as to Walter Edward Dandy (1886-1946) who developed the ventriculography (1918) and pneumoencephalography (1919) techniques. Pneumoencephalography was applied broadly up to the late 1970s, when it was replaced by less invasive and more accurate neuroimaging techniques.

We developed the bitterling as a unique, well-studied model organism in the area of the evolutionary ecology of brood parasitism. The bitterling-mussel relationship, interspecific mussel host preference, and mussel gill structure are studied in detail, to help understand the developmental adaptation of bitterling embryos in response to their mussel hosts. Our complete stage series of the bitterling species R. ocellatus in Chapter 2 is a new, character-based systems that are compatible with the widely-used zebrafish staging system. With time-lapse video, we demonstrated the dynamic processes of hatching moment of the rosy bitterling in real time, which indicates the hatching process is mechanical rather than enzymatic. In Chapter 3, we described the neuroanatomy of bitterling for the first time, filling the gaps in the previous embryonic research in various bitterling taxa. Combined with the molecular analysis of brain early development in Chapter 4, brain development in the rosy bitterling is compared with that in the zebrafish. In Chapter 5, we studied the morphogenetic process of blastokinesis in the bitterling embryo, and its possible relation to brood parasitism.

Schizencephaly is a rare congenital anomaly of the brain secondary to neuronal migration defect, characterized by slit or cleft in the cerebral hemispheres running from the pia to lateral ventricles. From clinical pint of view most of the patients present with different level of motor and psychological disorders. Imaging (CT-Scan and MRI) plays a key role in the definite diagnosis by which associated central nervous system (CNS) anomalies (absence of septum pellucidum and corpus callosum dysgenesis) could be diagnosed as well. Here, we present a case of 22 months old aphasic child suffering from head enlargement. CT-Scan image revealed unilateral schizencephaly compressing lateral ventricles and causing ventriculomegaly. We applied ventriculoperitoneal shunt (V–P shunt). After one month follow-up and brain repeated CT-Scan image for confirmation, the size of brain ventricles considerably diminished.

In mammals, multiciliated cells (MCCs) line the lumen of the trachea, oviduct, and brain ventricles, where they drive fluid flow across the epithelium. Each MCC population experiences vastly different local environments that may dictate differences in their lifetime and turnover rates. However, with the exception of MCCs in the trachea, the turnover rates of these multiciliated epithelial populations at extended time scales are not well described. Here, using genetic lineage-labeling techniques we provide a direct comparison of turnover rates of MCCs in these three different tissues. We find that oviduct turnover is similar to that in the airway (∼6 months), while multiciliated ependymal cells turnover more slowly.

We studied the distribution of the main astrocyte markers (glutamine synthetase, glial fibrillary acidic protein, connexin 43) in the tanycytes of the third ventricle during postnatal development. Using immunohistochemical methods, we analyzed the brain sections of Wistar rats at each of the following postnatal ages: day 7 (n = 4), day 30 (n = 4), 4–6 months (n = 8), and 20 months (n = 4). It was found that the tanycytes undergo cytochemical and structural changes during postnatal development and aging. Tanycyte differentiation in the lining of the third ventricle occurs in the first postnatal week. The protein profile typical of adult rat tanycytes is formed during the first month of postnatal development. The cytochemical profile of tanycytes does not change with age, but the tanycyte processes are reorganized. The data will help to establish the role of studied proteins in the development, formation, and aging of tanycytes in the third ventricle.

Background Cerebrospinal fluid (CSF) is an ultra-filtrated colorless brain fluid that circulates within brain spaces like the ventricular cavities, subarachnoid space, and the spine. Its continuous flow serves many primary functions, including nourishment, brain protection, and waste removal. Main body The abnormal accumulation of CSF in brain cavities triggers severe hydrocephalus. Accumulating evidence had indicated that synchronized beats of motile cilia (cilia from multiciliated cells or the ependymal lining in brain ventricles) provide forceful pressure to generate and restrain CSF flow and maintain overall CSF circulation within brain spaces. In humans, the disorders caused by defective primary and/or motile cilia are generally referred to as ciliopathies. The key role of CSF circulation in brain development and its functioning has not been fully elucidated. Conclusions In this review, we briefly discuss the underlying role of motile cilia in CSF circulation and hydrocephalus. We have reviewed cilia and ciliated cells in the brain and the existing evidence for the regulatory role of functional cilia in CSF circulation in the brain. We further discuss the findings obtained for defective cilia and their potential involvement in hydrocephalus. Furthermore, this review will reinforce the idea of motile cilia as master regulators of CSF movements, brain development, and neuronal diseases.

Motile cilia defects impair cerebrospinal fluid (CSF) flow, and can cause brain and spine disorders. To date, the development of ciliated cells, their impact on CSF flow and their function in brain and axial morphogenesis are not fully understood. Here, we have characterized motile ciliated cells within the zebrafish brain ventricles. We show that the ventricular surface undergoes significant restructuring through development, involving a transition from mono- to multiciliated cells (MCCs) driven by gmnc. MCCs are translationally polarized, co-exist with monociliated cells and generate directional flow patterns. Moreover, these ciliated cells have different developmental origins, and are genetically heterogenous with respect to expression of the Foxj1 family of ciliary master regulators. Finally, we show that cilia loss from specific brain regions or global perturbation of multiciliation does not affect overall brain or spine morphogenesis, but results in enlarged ventricles. Our findings establish that motile ciliated cells are generated by complementary and sequential transcriptional programs to support ventricular development.

Resumen Se presenta el caso de un paciente de 22 años sin antecedentes mórbidos que desarrolló un absceso cerebral secundario a una endocarditis por Eikenella corrodens. El diagnóstico se estableció mediante la detección por reacción de polimerasa en cadena universal en el líquido de la colección cerebral. La ecocardiografía transesofágica confirmó vegetaciones en la válvula mitral. Requirió la colocación de una derivación ventricular externa por vaciamiento del absceso a ventrículos cerebrales e hidrocefalia secundaria. Recibió 80 días de tratamiento antibacteriano efectivo. Su evolución fue favorable, con resolución completa de la infección verificada con imágenes y ecocardiografía de control. El seguimiento a los siete meses por una disfunción de válvula de drenaje ventrículo-peritoneal no demostró infección.

Brain midline delineates the boundary between the two cerebral hemispheres of the human brain, which plays a significant role in guiding intracranial hemorrhage surgery. Large midline shift caused by hematomas remains an inherent challenge for delineation. However, most previous methods only handle normal brains and delineate the brain midline on 2D CT images. In this study, we propose a novel hemisphere-segmented framework (HSF) for generating smooth 3D brain midline especially when large hematoma shifts the midline. Our work has four highlights. First, we propose to formulate the brain midline delineation as a 3D hemisphere segmentation task, which recognizes the midline location via enriched anatomical features. Second, we employ a distance-weighted map for midline aware loss. Third, we introduce rectificative learning for the model to handle various head poses. Finally, considering the complexity of hematomas distribution in human brain, we build a classification model to automatically identify the situation when hematoma breaks into brain ventricles and formulate a midline correction strategy to locally adjust the midline according to the location and boundary of hematomas. To our best knowledge, it is the first study focusing on delineating the brain midline on 3D CT images of hematoma patients and handling the situation of ventricle break-in. Through extensive validations on a large in-house dataset, our method outperforms state-of-the-art methods in various evaluation metrics.

Background Circumventricular organs (CVOs) are small structures without a blood–brain barrier surrounding the brain ventricles that serve homeostasic functions and facilitate communication between the blood, cerebrospinal fluid and brain. Secretory CVOs release peptides and sensory CVOs regulate signal transmission. However, pathogens may enter the brain through the CVOs and trigger neuroinflammation and neurodegeneration. We investigated the feasibility of dynamic contrast-enhanced (DCE) MRI to assess the CVO permeability characteristics in vivo, and expected significant contrast uptake in these regions, due to blood–brain barrier absence. Methods Twenty healthy, middle-aged to older males underwent brain DCE MRI. Pharmacokinetic modeling was applied to contrast concentration time-courses of CVOs, and in reference to white and gray matter. We investigated whether a significant and positive transfer from blood to brain could be measured in the CVOs, and whether this differed between secretory and sensory CVOs or from normal-appearing brain matter. Results In both the secretory and sensory CVOs, the transfer constants were significantly positive, and all secretory CVOs had significantly higher transfer than each sensory CVO. The transfer constants in both the secretory and sensory CVOs were higher than in the white and gray matter. Conclusions Current measurements confirm the often-held assumption of highly permeable CVOs, of which the secretory types have the strongest blood-to-brain transfer. The current study suggests that DCE MRI could be a promising technique to further assess the function of the CVOs and how pathogens can potentially enter the brain via these structures. Trial registration: Netherlands Trial Register number: NL6358, date of registration: 2017-03-24

Cerebrospinal fluid contacting neurons (CSF-cNs) represent a specific class of neurons located in close vicinity of brain ventricles and central canal. In contrast with knowledge gained from other vertebrate species, we found that vast majority of CSF-cNs in the spinal cord of C57Bl/6N mice is located in ectopic distal ventral position. However, we found that small number of ectopic CSF-cNs is present also in spinal cord of other investigated experimental mice strains (C57Bl/6J, Balb/C) and mammalian species (Wistar rats, New Zealand White rabbits). Similarly, as the proximal populations, ectopic CSF-cNs retain PKD2L1-immunoreactivity and synaptic contacts with other neurons. On the other side, they show rather multipolar morphology lacking thick dendrite contacting central canal lumen. Ectopic CSF-cNs in the spinal cord of C57Bl/6N mice emerge during whole period devoted to production of CSF-cNs and reach their ventral destinations during first postnatal weeks. In order to identify major gene, whose impairment could trigger translocation of CSF-cNs outside the central canal area, we took advantage of close consanguinity of C57Bl/6J substrain with normal CSF-cN distribution and C57Bl/6N substrain with majority of CSF-cNs in ectopic position. Employing in silico analyses, we ranked polymorphisms in C57Bl/6N substrain and selected genes Crb1, Cyfip2, Adamts12, Plk1, and Herpud2 as the most probable candidates, whose product dysfunction might be responsible for the ectopic distribution of CSF-cNs. Furthermore, segregation analysis of F2 progeny of parental C57Bl/6N and Balb/C mice revealed that polymorphic loci of Crb1 and Cyfip2 underlie the ectopic position of CSF-cNs in the spinal cord of C57Bl/6N mice.

We have applied a deep learning framework, trained on mouse embryo images acquired with a 40 MHz annular array, to volumetric data acquired with a VisualSonics Vevo 3100 commercial scanner using a 40-MHz linear array. The deep learning framework was robust enough to accurately segment out the body and the brain ventricle from the 3D data generated by the commercial scanner. These results show that there is no need to retrain the algorithm with hundreds of new manually segmented datasets.

Convection-enhanced delivery is a technique to bypass the blood–brain barrier and deliver therapeutic drugs into the brain tissue. However, animal investigations and preliminary clinical trials have reported reduced efficacy to transport the infused drug in specific zones, attributed mainly to backflow, in which an annular gap is formed outside the catheter and the fluid preferentially flows toward the surface of the brain rather than through the tissue in front of the cannula tip. In this study, a three-dimensional human brain finite element model of backflow was developed to study the influence of anatomical structures during flow-controlled infusions. Predictions of backflow length were compared under the influence of ventricular pressure and the distance between the cannula and the ventricles. Simulations with zero relative ventricle pressure displayed similar backflow length predictions for larger cannula-ventricle distances. In addition, infusions near the ventricles revealed smaller backflow length and the liquid was observed to escape to the longitudinal fissure and ventricular cavities. Simulations with larger cannula-ventricle distances and nonzero relative ventricular pressure showed an increase of fluid flow through the tissue and away from the ventricles. These results reveal the importance of considering both the subject-specific anatomical details and the nonlinear effects in models focused on analyzing current and potential treatment options associated with convection-enhanced delivery optimization for future clinical trials.

Objectives The ependymal lining of the human brain ventricular system displays distinct structural differences and functional heterogeneity among individual ependymal cells (ECs). To date, multi-ciliated ECs (E1 cells), bi-ciliated ECs (E2 cells), uni-ciliated ECs (E3 cells), ECs without cilia, and ECs with cytoplasmic protrusions have been described in human brain ventricles. Method Using scanning electron microscopy (SEM), we evaluated ependymal samples from 6 defined regions of the third ventricle from 9 human brains. These regions were strictly defined according to the periventricular structures they neighbour with. Results We observed different structures on the apical surface of the ECs. Various ECs differed from each other by the presence of microvilli, secretory bodies, and a variable number of cilia, which led us to divide the ECs into several exactly specified types according to their apical morphology. Conclusion We found all types of ECs in every examined region with a predominance of particular types of apical surface of ECs in the individual areas (Tab. 4, Fig. 7, Ref. 22).

The choroid plexus (ChP) produces cerebrospinal fluid and forms a critical barrier between the brain and the circulation. While the ChP forms in each brain ventricle, it adopts a different shape in each one and remarkably little is known about the mechanisms underlying its development. Here, we show that epithelial WNT5A is critical for determining fourth ventricle (4V) ChP morphogenesis and size. SystemicWnt5aknockout, or forced WNT5A overexpression beginning at E10.5, profoundly reduced the size and development of ChP in all ventricles. However, conditional deletion ofWnt5aexpression inFoxj1-expressing epithelial cells affected only the branched, villous morphology of the 4V ChP. We found that WNT5A was enriched in epithelial cells localized to the distal tips of 4V ChP villi, where WNT5A acted locally to activate non-canonical Wnt signaling via Ror1/Ror2 receptors. During 4V ChP development, MEIS1 bound to the proximalWnt5apromoter, and gain- and loss-of-function approaches demonstrated that MEIS1 regulatedWnt5aexpression. Collectively, our findings demonstrate a dual function of WNT5A in ChP development and identify MEIS1 and MEIS2 as upstream regulators ofWnt5ain the 4V ChP epithelium.

The ependymal lining of the walls of the human brain third ventricle (3v), fourth ventricle (4v) and aqueductus cerebri (A) was studied. For a better localization of different ependymal areas, they were labelled by periventricular structures that represent a basic and stable part of brain nerve tissue and they are localized most closely to ventricle walls. Labelling of individual ependymal areas of the ventricle walls was composed of the number of a brain ventricle, letters: E – ependyma and abbreviation of a Latin name of the periventricular structure, e.g., the corpus mammillare is “CM“. Labelling of ependyma over the corpus mammillare is” 3vE – CM “Results of labelling of ependymal areas were arranged in the form of tables called “ependymal table “(ET), i.e., ET for 3v; ET for 4v; ET for A. It is believed that labelling of individual ependymal areas according to periventricular structures could be useful for unambiguous labelling of ependyma of the ventricle walls and will help to a mutual comparison of the same types of ependymal areas studied by various authors.

By engaging angiotensin-converting enzyme 2 (ACE2 or Ace2), the novel pathogenic SARS-coronavirus 2 (SARS-CoV-2) may invade host cells in many organs, including the brain. However, the distribution of ACE2 in the brain is still obscure. Here we investigated the ACE2 expression in the brain by analyzing data from publicly available brain transcriptome databases. According to our spatial distribution analysis, ACE2 was relatively highly expressed in some brain locations, such as the choroid plexus and paraventricular nuclei of the thalamus. According to cell-type distribution analysis, nuclear expression of ACE2 was found in many neurons (both excitatory and inhibitory neurons) and some non-neuron cells (mainly astrocytes, oligodendrocytes, and endothelial cells) in human middle temporal gyrus and posterior cingulate cortex. A few ACE2-expressing nuclei were found in a hippocampal dataset, and none were detected in the prefrontal cortex. Except for the additional high expression of Ace2 in the olfactory bulb areas for spatial distribution as well as in the pericytes and endothelial cells for cell-type distribution, the distribution of Ace2 in mouse brain was similar to that in the human brain. Thus, our results reveal an outline of ACE2/Ace2 distribution in the human and mouse brain, which indicates the brain infection of SARS-CoV-2 may be capable of inducing central nervous system symptoms in coronavirus disease 2019 (COVID-19) patients. Potential species differences should be considered when using mouse models to study the neurological effects of SARS-CoV-2 infection.

The segmentation of the brain ventricle (BV) and body in embryonic mice high-frequency ultrasound (HFU) volumes can provide useful information for biological researchers. However, manual segmentation of the BV and body requires substantial time and expertise. This work proposes a novel deep learning based end-to-end auto-context refinement framework, consisting of two stages. The first stage produces a low resolution segmentation of the BV and body simultaneously. The resulting probability map for each object (BV or body) is then used to crop a region of interest (ROI) around the target object in both the original image and the probability map to provide context to the refinement segmentation network. Joint training of the two stages provides significant improvement in Dice Similarity Coefficient (DSC) over using only the first stage (0.818 to 0.906 for the BV, and 0.919 to 0.934 for the body). The proposed method significantly reduces the inference time (102.36 to 0.09 s/volume ≈1000x faster) while slightly improves the segmentation accuracy over the previous methods using slide-window approaches.

Introduction Brain ventricles are dilated with accumulation of excess cerebrospinal fluid in it, which can cause the pressure damage to the surrounding structures. This study aims to highlight the reference range values for lateral and third ventricles of brain for easy diagnosis and management of hydrocephalic patients. Material and methods We calculated the frontal horn ratio(FHR), bi- caudate ratio(BCR), Evan’s ratio(ER), cella media ratio(CMR), bi-frontal index(BFI), bi- occipital index(BOI), third ventricle width(TVW), third ventricle sylvian fissure ratio index (TSFI), and third ventricle ratio (TVR) in 120 apparently normal CT-Head images and forty hydrocephalic images by taking linear measurements withdicom image software. Descriptive statistics –mean, standard deviation, standard error, 95% confidence interval were calculated for each parameter. Independent student t- test, age regression analysis, and Spearman’s rank correlation coefficient were applied accordingly. Results BCR, ER, TSFI showed significant correlation with the age and anteroposterior diameter of brain. BCR and TVW were significantly higher in males. In normal images, 95% confidence limits for FHR [0.295-0.309], TVW [6.104–6.92], TSFI [0.538–0.558] were found. The mean FHR and TVR in hydrocephalic patients were 0.42 and 0.072. Discussion Since Frontal horn ratio and Third ventricle ratio do not depend upon the age, sex and size of brain, these two parameters can be used as the screening and monitoring tools in patients with hydrocephalus.

Vascular plexus of the ventricles of the brain play an important role in the formation of liquor, involved in the exchange, trophic, protective, homeostatic function of the brain. The role of the vascular component of the choroid plexus is not fully understood. The authors studied age-related changes in the vascular component of ventricular plexus in rats. The revealed involutional changes may be the cause of some brain diseases, accompanied by a disorder of the synthesis of cerebrospinal fluid

Radionuclide scanning images published inNatureby Di Chiro in 1964 showed a downward migration along the spinal canal of particle tracers injected in the brain ventricles while also showing an upward flow of tracers injected in the lumbar region of the canal. These observations, since then corroborated by many radiological measurements, have been the basis for the hypothesis that there must be an active circulation mechanism associated with the transport of cerebrospinal fluid (CSF) deep down into the spinal canal and subsequently returning a portion back to the cranial vault. However, to date, there has been no physical explanation for the mechanism responsible for the establishment of such a bulk recirculating motion. To investigate the origin and characteristics of this recirculating flow, we have analyzed the motion of the CSF in the subarachnoid space of the spinal canal. Our analysis accounts for the slender geometry of the spinal canal, the small compliance of the dura membrane enclosing the CSF in the canal, and the fact that the CSF is confined to a thin annular subarachnoid space surrounding the spinal cord. We apply this general formulation to study the characteristics of the flow generated in a simplified model of the spinal canal consisting of a slender compliant cylindrical pipe with a coaxial cylindrical inclusion, closed at its distal end, and subjected to small periodic pressure pulsations at its open entrance. We show that the balance between the local acceleration and viscous forces produces a leading-order flow consisting of pure oscillatory motion with axial velocities on the order of a few centimetres per second and amplitudes monotonically decreasing along the length of the canal. We then demonstrate that the nonlinear term associated with the convective acceleration contributes to a second-order correction consisting of a steady streaming that generates a bulk recirculating motion of the CSF along the length of the canal with characteristic velocities two orders of magnitude smaller than the leading-order oscillatory flow. The results of the analysis of this idealized geometry of the spinal canal are shown to be in good agreement not only with experimental measurements in anin-vitromodel but also with radiological measurements conducted in human adults.