Syringomyelia hydrodynamics: an in vitro study based on in vivo measurements

A simplified in vitro model of the spinal canal, based on in vivo magnetic resonance imaging, was used to examine the hydrodynamics of the human spinal cord and subarachnoid space with syringomyelia. In vivo magnetic resonance imaging (MRI) measurements of subarachnoid (SAS) geometry and cerebrospinal fluid velocity were acquired in a patient with syringomyelia and used to aid in the in vitro model design and experiment. The in vitro model contained a fluid-filled coaxial elastic tube to represent a syrinx. A computer controlled pulsatile pump was used to subject the in vitro model to a CSF flow waveform representative of that measured in vivo. Fluid velocity was measured at three axial locations within the in vitro model using the same MRI scanner as the patient study. Pressure and syrinx wall motion measurements were conducted external to the MR scanner using the same model and flow input. Transducers measured unsteady pressure both in the SAS and intra-syrinx at four axial locations in the model A laser Doppler vibrometer recorded the syrinx wall motion at 18 axial locations and three polar positions. Results indicated that the peak-to-peak amplitude of the SAS flow waveform in vivo was approximately tenfold that of the syrinx and in phase (SAS approximately 5.2 +/- 0.6 ml/s, syrinx approximately 0.5 +/- 0.3 ml/s). The in vitro flow waveform approximated the in vivo peak-to-peak magnitude (SAS approximately 4.6 +/- 0.2 ml/s, syrinx approximately 0.4 +/- 0.3 ml/s). Peak-to-peak in vitro pressure variation in both the SAS and syrinx was approximately 6 mm Hg. Syrinx pressure waveform lead the SAS pressure waveform by approximately 40 ms. Syrinx pressure was found to be less than the SAS for approximately 200 ms during the 860-ms flow cycle. Unsteady pulse wave velocity in the syrinx was computed to be a maximum of approximately 25 m/s. LDV measurements indicated that spinal cord wall motion was nonaxisymmetric with a maximum displacement of approximately 140 microm, which is below the resolution limit of MRI. Agreement between in vivo and in vitro MR measurements demonstrates that the hydrodynamics in the fluid filled coaxial elastic tube system are similar to those present in a single patient with syringomyelia. The presented in vitro study of spinal cord wall motion, and complex unsteady pressure and flow environment within the syrinx and SAS, provides insight into the complex biomechanical forces present in syringomyelia.     

The origins of syringomyelia: numerical models of fluid/structure interactions in the spinal cord

A two-dimensional axi-symmetric numerical model is constructed of the spinal cord, consisting of elastic cord tissue surrounded by aqueous cerebrospinal fluid, in turn surrounded by elastic dura. The geometric and elastic parameters are simplified but of realistic order, compared with existing measurements. A distal reflecting site models scar tissue formed by earlier trauma to the cord, which is commonly associated with syrinx formation. Transients equivalent to both arterial pulsation and percussive coughing are used to excite wave propagation. Propagation is investigated in this model and one with a central canal down the middle of the cord tissue, and in further idealized versions of it, including a model with no cord, one with a rigid cord, one with a rigid dura, and a double-length untapered variant of the rigid-dura model. Analytical predictions for axial and radial wave-speeds in these different situations are compared with, and used to explain, the numerical outcomes. We find that the anatomic circumstances of the spinal cerebrospinal fluid cavity probably do not allow for significant wave steepening phenomena. The results indicate that wave propagation in the real cord is set by the elastic properties of both the cord tissue and the confining dura mater, fat, and bone. The central canal does not influence the wave propagation significantly.     

Pressure wave propagation in fluid-filled co-axial elastic tubes. Part 2: Mechanisms for the pathogenesis of syringomyelia

Our aim in this paper is to use a simple theoretical model of the intraspinal cerebrospinal-fluid system to investigate mechanisms proposed for the pathogenesis of syringomyelia. The model is based on an inviscid theory for the propagation of pressure waves in co-axial, fluid-filled, elastic tubes. According to this model, the leading edge of a pressure pulse tends to steepen and form an elastic jump, as it propagates up the intraspinal cerebrospinal-fluid system. We show that when an elastic jump is incident on a stenosis of the spinal subarachnoid space, it reflects to form a transient, localized region of high pressure within the spinal cord that for a cough-induced pulse is estimated to be 50 to 70 mm Hg or more above the normal level in the spinal subarachnoid space. We propose this as a new mechanism whereby pressure pulses created by coughing or sneezing can generate syrinxes. We also use the same analysis to investigate Williams' suck mechanism. Our results do not support his concept, nor, in cases where the stenosis is severe, the differential-pressure-propagation mechanism recently proposed by Greitz et al. Our analysis does provide some support for the piston mechanism recently proposed by Oldfield et al. and Heiss et al. For instance, it shows clearly how the spinal cord is compressed by the formation of elastic jumps over part of the cardiac cycle. What appears to be absent for this piston mechanism is any means whereby the elastic jumps can be focused (e.g., by reflecting from a stenosis) to form a transient, localized region of high pressure within the spinal cord. Thus it would seem to offer a mechanism for syrinx progression, but not for its formation.     

Spinal subarachnoid space pressure measurements in an in vitro spinal stenosis model: implications on syringomyelia theories

Full explanation for the pathogenesis of syringomyelia (SM), a neuropathology characterized by the formation of a cystic cavity (syrinx) in the spinal cord (SC), has not yet been provided. It has been hypothesized that abnormal cerebrospinal fluid (CSF) pressure, caused by subarachnoid space (SAS) flow blockage (stenosis), is an underlying cause of syrinx formation and subsequent pain in the patient. However, paucity in detailed in vivo pressure data has made theoretical explanations for the syrinx difficult to reconcile. In order to understand the complex pressure environment, four simplified in vitro models were constructed to have anatomical similarities with post-traumatic SM and Chiari malformation related SM. Experimental geometry and properties were based on in vivo data and incorporated pertinent elements such as a realistic CSF flow waveform, spinal stenosis, syrinx, flexible SC, and flexible spinal column. The presence of a spinal stenosis in the SAS caused peak-to-peak cerebrospinal fluid CSF pressure fluctuations to increase rostral to the stenosis. Pressure with both stenosis and syrinx present was complex. Overall, the interaction of the syrinx and stenosis resulted in a diastolic valve mechanism and rostral tensioning of the SC. In all experiments, the blockage was shown to increase and dissociate SAS pressure, while the axial pressure distribution in the syrinx remained uniform. These results highlight the importance of the properties of the SC and spinal SAS, such as compliance and permeability, and provide data for comparison with computational models. Further research examining the influence of stenosis size and location, and the importance of tissue properties, is warranted.     

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

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

Cellular dynamics and tissue interactions of the dura mater during head development

During development and growth of the neurocranium, the dura mater regulates events in the underlying brain and overlying skull by the release of soluble factors and cellular activity. Morphogenesis of the cranial bones and sutures is dependent on tissue interactions with the dura mater, which control the size and shape of bones as well as sutural patency. Development of the brain also involves interactions with dura mater: secretion of stromal derived factor 1 (SDF-1) is a critical event in directing migration of the external granular layer precursors of the cerebellar cortex and the Cajal-Retzius (CR) cells of the cerebral cortex. The dura mater is also required for growth of the hippocampal dentate gyrus. Wnt1Cre/R26R transgenic reporter mice were used to study the origin and fates of the cells of dura mater during head development. The dura mater of mammals is derived entirely from the cranial neural crest. Beginning around neonatal day 10 (N 10), the dura mater is infiltrated by cells derived from paraxial mesoderm, which later come to predominate. Over the course of infancy, the neural crest-derived cells of the dura mater become sequestered in niche-like distribution characteristic of stem cells. Simultaneously, dura mater cells underlying the sagittal suture migrate upward into the mesodermally-derived mesenchyme separating the parietal bones. Although initially the parietal bones are formed entirely from paraxial mesoderm, the cellular composition gradually becomes chimeric and is populated mainly by neural crest-derived cells by N 30. This occurs as a consequence of osteoblastic differentiation at the dura mater interface and intravasation of neural crest-derived osteoclastic and other hematopoietic precursors. The isolated cells of the dura mater are multipotent in vitro, giving rise to osteoblasts, neuronal cells and other derivatives characteristic of cranial neural crest, possibly reflecting the multipotent nature of dura mater cells in vivo.     

Syrinx fluid transport: modeling pressure-wave-induced flux across the spinal pial membrane

Syrinxes are fluid-filled cavities of the spinal cord that characterize syringomyelia, a disease involving neurological damage. Their formation and expansion is poorly understood, which has hindered successful treatment. Syrinx cavities are hydraulically connected with the spinal subarachnoid space (SSS) enveloping the spinal cord via the cord interstitium and the network of perivascular spaces (PVSs), which surround blood vessels penetrating the pial membrane that is adherent to the cord surface. Since the spinal canal supports pressure wave propagation, it has been hypothesized that wave-induced fluid exchange across the pial membrane may play a role in syrinx filling. To investigate this conjecture a pair of one-dimensional (1-d) analytical models were developed from classical elastic tube theory coupled with Darcy's law for either perivascular or interstitial flow. The results show that transpial flux serves as a mechanism for damping pressure waves by alleviating hoop stress in the pial membrane. The timescale ratio over which viscous and inertial forces compete was explicitly determined, which predicts that dilated PVS, SSS flow obstructions, and a stiffer and thicker pial membrane-all associated with syringomyelia-will increase transpial flux and retard wave travel. It was also revealed that the propagation of a pressure wave is aided by a less-permeable pial membrane and, in contrast, by a more-permeable spinal cord. This is the first modeling of the spinal canal to include both pressure-wave propagation along the spinal axis and a pathway for fluid to enter and leave the cord, which provides an analytical foundation from which to approach the full poroelastic problem.     

Nasal capsular cartilage is required for rat transpalatal suture morphogenesis

In the cranial vault, suture morphogenesis occurs when the growing cranial bones approximate and overlap or abut one another. Patency of developing sutures is regulated by the underlying dura mater. Once cranial sutures form, bone growth proceeds from the sutures in response to growth signals from the rapidly expanding neurocranium. Facial sutures do not develop in contact with the dura mater. It was therefore hypothesized that facial suture morphogenesis and bone growth from facial sutures are regulated by tissues with an equivalent role to the dura mater. The present study was designed to test this hypothesis by characterizing the morphology and growth factor expression in developing transpalatal (TP) sutures and their surrounding tissues, and then assessing the role of the overlying nasal capsular (NC) cartilages in maintaining suture patency. TP sutures develop as overlapping sutures, similar to cranial coronal sutures, and expression of Tgf-betas in TP sutures was similar to their distribution in cranial coronal sutures. To establish whether NC cartilages play a role in regulating TP suture morphogenesis, fetal rat TP sutures were cultured with associated attached NC cartilages or with NC cartilages removed. Sutures cultured for upward of 5 days with intact NC cartilages remained patent and maintained their cellular and fibrous components. However, in the absence of NC cartilages, the cellular nature of the sutures was not maintained and they became progressively acellular, with bony bridging across the suture. This finding is similar to that for cranial vault sutures cultured in the absence of dura mater, indicating that NC cartilages play an equivalent role to dura mater in maintaining the patency of developing sutures. These studies indicate that tissue interactions likely regulate morphogenesis of all cranial and facial sutures.     

A one-dimensional model of the spinal cerebrospinal-fluid compartment

Modeling of the cerebrospinal fluid (CSF) system in the spine is strongly motivated by the need to understand the origins of pathological conditions such as the emergence and growth of fluid-filled cysts in the spinal cord. In this study, a one-dimensional (1D) approximation for the flow in elastic conduits was used to formulate a model of the spinal CSF compartment. The modeling was based around a coaxial geometry in which the inner elastic cylinder represented the spinal cord, middle elastic tube represented the dura, and the outermost tube represented the vertebral column. The fluid-filled annuli between the cord and dura, and the dura and vertebral column, represented the subarachnoid and epidural spaces, respectively. The system of governing equations was constructed by applying a 1D form of mass and momentum conservation to all segments of the model. The developed 1D model was used to simulate CSF pulse excited by pressure disturbances in the subarachnoid and epidural spaces. The results were compared to those obtained from an equivalent two-dimensional finite element (FE) model which was implemented using a commercial software package. The analysis of linearized governing equations revealed the existence of three types of waves, of which the two slower waves can be clearly related to the wave modes identified in previous similar studies. The third, much faster, wave emanates directly from the vertebral column and has little effect on the deformation of the spinal cord. The results obtained from the 1D model and its FE counterpart were found to be in good general agreement even when sharp spatial gradients of the spinal cord stiffness were included; both models predicted large radial displacements of the cord at the location of an initial cyst. This study suggests that 1D modeling, which is computationally inexpensive and amenable to coupling with the models of the cranial CSF system, should be a useful approach for the analysis of some aspects of the CSF dynamics in the spine. The simulation of the CSF pulse excited by a pressure disturbance in the epidural space, points to the possibility that regions of the spinal cord with abnormally low stiffness may be prone to experiencing large strains due to coughing and sneezing.     

Dura mater-derived FGF-2 mediates mitogenic signaling in calvarial osteoblasts

Although dura mater tissue is believed to have an important role in calvarial reossification in many in vivo studies, few studies have shown the direct effect of dura mater cells on osteoblasts. In addition, no reports have yet identified the potential factor(s) responsible for various biological activities exerted by dura mater on calvarial reossification (e.g., cell proliferation). In this study, we tested the effect of dura mater on calvarial-derived osteoblasts by performing both heterotypic coculture and by culturing osteoblast cells with conditioned media harvested from dura mater cells of juvenile (3-day-old) and adult (30-day-old) mice. The results presented here demonstrate that cellular proliferation of juvenile osteoblast cells was significantly increased by juvenile dura mater either in the coculture system or when dura mater cell-conditioned medium was applied to the osteoblast cells. Moreover, high levels of FGF-2 protein were detected in juvenile dura mater cells and their conditioned medium. In contrast, low levels of FGF-2 protein were detected in adult dura mater cells, whereas FGF-2 protein was not detectable in their conditioned medium. Abrogation of the mitogenic effect induced by juvenile dura mater cell-conditioned medium was achieved by introducing a neutralizing anti-FGF-2 antibody, thus indicating that FGF-2 may be responsible for the mitogenic effect of the juvenile dura mater. Moreover, data obtained by exploring the three major FGF-2 signaling pathways further reinforced the idea that FGF-2 might be an important paracrine signaling factor in vivo supplied by the underlying dura mater to the overlying calvarial osteoblasts.     

Systematic review and meta-analysis of the biomechanical properties of the human dura mater applicable in computational human head models

Accurate biomechanical properties of the human dura mater are required for computational models and to fabricate artificial substitutes for transplantation and surgical training purposes. Here, a systematic literature review was performed to summarize the biomechanical properties of the human dura mater that are reported in the literature. Furthermore, anthropometric data, information regarding the mechanically tested samples, and specifications with respect to the used mechanical testing setup were extracted. A meta-analysis was performed to obtain the pooled mean estimate for the elastic modulus, ultimate tensile strength, and strain at maximum force. A total of 17 studies were deemed eligible, which focused on human cranial and spinal dura mater in 13 and 4 cases, respectively. Pooled mean estimates for the elastic modulus (n?=?448), the ultimate tensile strength (n?=?448), and the strain at maximum force (n?=?431) of 68.1 MPa, 7.3 MPa and 14.4% were observed for native cranial dura mater. Gaps in the literature related to the extracted data were identified and future directions for mechanical characterizations of human dura mater were formulated. The main conclusion is that the most commonly used elastic modulus value of 31.5 MPa for the simulation of the human cranial dura mater in computational head models is likely an underestimation and an oversimplification given the morphological diversity of the tissue in different brain regions. Based on the here provided meta-analysis, a stiffer linear elastic modulus of 68 MPa was observed instead. However, further experimental data are essential to confirm its validity.

     

Proliferation rate of human osteoblast-like cells on alloplastic biomaterials and their clinical application for the transnasal duraplasty procedure

The possibility of transmission of slow virus infection (HIV) and Creutzfeld-Jakob disease by cadaveric dura implants makes it necessary to find synthetic, absorbable materials for the reconstruction of the dura mater. Various procedures with autologous or alloplastic material are described. Four commercially available biomaterials were choosen to study the proliferation rate and the biocompatibility of human osteoblast-like cells (HOB-like cells) on 2- dimensional material by biochemical analysis. With a proliferation assay, the viability and the proliferation capacity of osteoblast-like cells were evaluated. A clinical trial was added to study resorbable fleece as one of the previously tested biomaterial in a small patient group (8 patients) to close anterior cranial fossa dura defects. The results of the proliferation assay showed the highest proliferation rate of HOB-like cells on resorbable fleece. All patients in our clinical trial with anterior cranial fossa dura defects were successfully treated with resorbable fleece. There was no evidence for persisting cerebrospinal fluid rhinorrhea or foreign body reaction after the period of wound healing. The present study demonstrated an excellent biocompatibility of resorbable fleece. The vicryl fleece is an alternative alloplastic material for endonasal closure of defined substantial defects of the dura with cerebrospinal fluid.     

Effect of bone fragment impact velocity on biomechanical parameters related to spinal cord injury: A finite element study

Several experimental and computational studies have investigated the effect of bone fragment impact on the spinal cord during trauma. However, the effect of the impact velocity of a fragment generated by a burst fracture on the stress and strain inside the spinal cord has not been computationally investigated, even though spinal canal occlusion and peak pressure at various impact velocities were provided in experimental studies. These stresses and strains are known factors related to clinical symptoms or injuries. In this study, a fluid-structure interaction model of the spinal cord, dura mater, and cerebrospinal fluid was developed and validated. The von-Mises stress distribution in the cord, the longitudinal strain, the cord compression and cross-sectional area at the impact center, and the obliteration of the cerebrospinal fluid layer were analyzed for three pellet sizes at impact velocities ranging from 1.5 m/s to 7.5 m/s. The results indicate that stress in the cord was substantially elevated when the initial impact velocity of the pellet exceeded a threshold of 4.5 m/s. Cord compression, reduction in cross-sectional area, and obliteration of the cerebrospinal fluid increased gradually as the velocity of the pellet increased, regardless of the size of the pellet. The present study provides insight into the mechanisms underlying spinal cord injury.     

The presence of arachnoiditis affects the characteristics of CSF flow in the spinal subarachnoid space: a modelling study

Syringomyelia is a neurological disorder characterised by high pressure fluid-filled cysts within the spinal cord. As syringomyelia is associated with abnormalities of the central nervous system that obstruct cerebrospinal fluid (CSF) flow, it is thought that changes in CSF dynamics play an important role in its pathogenesis. Using three-dimensional computational models of the spinal subarachnoid space (SAS), this study aims to determine SAS obstructions, such as arachnoiditis, change in CSF dynamics in the SAS. The geometry of the SAS was reconstructed from a series of MRI images. CSF is modelled as an incompressible Newtonian fluid with a dynamic viscosity of 1 mPa s. Three computational models simulated CSF flow in either the unobstructed SAS, or with the SAS obstructed by a porous region simulating dorsal or circumferential arachnoiditis. The permeability of this porous obstruction was varied for the model with dorsal arachnoiditis. The results show that arachnoiditis increases flow resistance in the SAS and this is accompanied by a modest increase in magnitude and/or shift in timing (with respect to the cardiac cycle) of the CSF pressure drop across the region of arachnoiditis. This study suggests that syrinx formation may be related to a change in temporal CSF pulse pressure dynamics.     

Effect of bioabsorbable osseous fixation materials on dura mater and brain tissue

Bioabsorbable materials are frequently used in pediatric cranial surgery, but the effects of these materials on neural tissue are not known. The authors assessed the histologic alterations to dura mater and brain tissue associated with bioabsorbable plates. Fifteen Sprague-Dawley rats were given sham cranial surgery; an additional 30 underwent placement of 8 x 8-mm polylactic acid/poly-glycolic acid plates. The rats were assessed weekly for neurologic or behavioral changes suggesting neural damage. A portion of each group was killed at 3, 6, and 12 months for histologic analysis of cranium, dura mater, and brain tissue by standard hematoxylin and eosin stain. None of the animals showed any behavioral changes or neurologic deficits. The plates were gradually hydrolyzed over the study period, and all had disappeared by 12 months. The histologic examination showed fibrous encapsulation around the plates, accompanied by foreign body giant cell reaction and calcification. Focal gliosis, where evident, was mild and confined primarily to the superficial cortex of the brain beneath the plate. The infiltration of the dura mater and underlying brain parenchyma was negligible. In conclusion, the neurologic and histologic effect of bioabsorbable plates on neural tissue may be considered negligible in the early postoperative period.     

Cranial suture obliteration is induced by removal of transforming growth factor (TGF)-beta 3 activity and prevented by removal of TGF-beta 2 activity from fetal rat calvaria in vitro

Cranial suture morphogenesis requires soluble, heparin-binding factors secreted by the dura mater to resist premature osseous obliteration. Elevated levels of transforming growth factor (TGF)-beta 1, TGF-beta 2, and TGF-beta 3 have previously been noted in cranial sutures undergoing normal and premature sutural obliteration. To examine the role of TGF-beta s in regulating cranial suture morphogenesis, an established in vitro, serum-free, calvarial culture system was used. In this system, fetal rat coronal sutures undergo apparently normal suture morphogenesis in the presence of dura mater, but undergo osseous obliteration in the absence of dura mater. Neutralizing polyclonal antibodies to TGF-beta 1, TGF-beta 2, or TGF-beta 3 were added to cultures of fetal day 19 rat calvaria, which were harvested at 3, 4, or 5 days, processed for histology, sectioned, and examined. Coronal sutures from calvaria cultured in the presence of dura mater resisted obliteration, either alone or in the presence of TGF-beta 1 or TGF-beta 2 neutralizing antibodies. However, sutures from calvaria cultured in the presence of TGF-beta 3 neutralizing antibodies became obliterated. Conversely, sutures from calvaria cultured in the absence of dura mater became obliterated by bone, either alone or in the presence of neutralizing antibodies to TGF-beta 1 or TGF-beta 3. However, those sutures cultured in the presence of neutralizing antibodies to TGF-beta 2 were rescued from osseous obliteration.     

An optofluidic mechanical system for elasticity measurement of thin biological tissues

As dura mater has an anisotropic fibrous structure and exists under wet and dynamic stretching conditions in the brain, its mechanical properties have not yet been properly investigated. Here we developed a fluid-assisted mechanical system integrated with a photonic sensor and a pressure sensor in order to measure the elasticity of the dura mater. Porcine dura mater sample was loaded as a stretched diaphragm into a liquid chamber to mimic the in vivo condition. Increasing the flow rate of saline solution into the chamber swelled and deformed the dura mater. The micron-scale deflection of the dura mater was optically detected by the photonic sensor. Fluid pressure and deflection values were then used to calculate the elastic modulus. The average elastic modulus of the porcine dura mater was 31.14 MPa. We further measured the elasticity of a well-known material to further validate the system. We expect that this optofluidic system developed in this study will be useful to measure the elasticity of a variety of thin biological tissues.     

清醒状态下电刺激大鼠上矢状窦模型后脑内Fos阳性神经元的分布

目的清醒状态下电刺激大鼠上矢状窦后免疫组织化学染色观察Fos阳性神经元在脑内的分布情况。方法雄性SD大鼠,手术暴露上矢状窦后电刺激硬脑膜,应用免疫组织化学染色技术观察Fos阳性神经元在脑内的分布并绘图。结果电刺激后Fos阳性神经元在脑内分布广泛,主要集中在高颈段脊髓后角,三叉脊束核尾侧亚核,中缝核簇,中脑导水管周围灰质,脚间核及下丘脑等区域。结论脑内的多个区域参与了偏头痛的发生和发展过程,除与疼痛的信息传递和调控有关外,与情感、植物神经等调控有关的核团也参与其中。     

Morphofunctional characteristics of the microcirculatory bed of the human spinal dura mater]

Some morphofunctional peculiarities in microcirculatory pathways of the dura mater of the human spinal cord are described. They are concerned with the structure of arteriolo-venular anastomoses through which a rather large amount of arterial blood is transported into the venous bed. Around the vessels of arterial type running at an angle to the longitudinal axis of the vessel connective tissue fibres of the dura mater, there is a tissue layer intensively impregnated with silver salts and stained PAS-positively. The venous part of the dura mater microcirculatory pathways has a large number of accessory reservoirs in the form of venous "lakes". Functional importance of the peculiarities mentioned above for the dura mater and the perimedullar apparatus is clarified.     

Sustained high-pressure in the spinal subarachnoid space while arterial expansion is low may be linked to syrinx development

Syringomyelia (a spinal cord cyst) usually develops as a result of conditions that cause cerebrospinal fluid (CSF) obstruction. The mechanism of syrinx formation and enlargement remains unclear, though previous studies suggest that the fluid enters via the perivascular spaces (PVS) of the penetrating arteries of the spinal cord, and that alterations in the CSF pulse timing and pressure could contribute to enhanced PVS inflow. This study uses an idealised computational model of the PVS to investigate the factors that influence peri-arterial fluid flow. First, we used three sample patient-specific models to explore whether changes in subarachnoid space (SAS) pressures in individuals with and without syringomyelia could influence PVS inflow. Second we conducted a parametric study to determine how features of the CSF pulse altered perivascular fluid, including alterations to timing and magnitude of the peak SAS pressure, the timing of reversal from high to low pressure (diastolic phase), and the area under the pressure–time curve. The model for the patient with syringomyelia had higher net CSF inflow to the PVS than the two subjects without syringomyelia. In the parametric study, only increasing the area under the high pressure region of the SAS pulse substantially increased PVS inflow, when coupled with a temporal shift in arterial and SAS pulses. This suggests that a period of sustained high SAS pressure while arterial diameter is low may increase net CSF pumping into the PVS.