Spinal Subarachnoid Space Pressure Measurements in an In Vitro Spinal Stenosis Model: Implications on Syringomyelia Theories

2010 ◽  
Vol 132 (11) ◽  
Author(s):  
Bryn A. Martin ◽  
Richard Labuda ◽  
Thomas J. Royston ◽  
John N. Oshinski ◽  
Bermans Iskandar ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Spinal Stenosis ◽  
Subarachnoid Space ◽  
Computational Models ◽  
Spinal Column ◽  
Valve Mechanism ◽  
Tissue Properties ◽  
Csf Pressure

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.

Pathological Biomechanics of Cerebrospinal Fluid Pressure in Syringomyelia: Fluid Structure Interaction of an In Vitro Coaxial Elastic Tube System

2009 ◽  
Author(s):  
Bryn A. Martin ◽  
Richard Labuda ◽  
Thomas J. Royston ◽  
John N. Oshinski ◽  
Bermans Iskandar ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cerebrospinal Fluid ◽  
Computational Models ◽  
Fluid Pressure ◽  
Theoretical Explanation ◽  
Elastic Tube ◽  
Tube System ◽  
Valve Mechanism

Full explanation for the formation and pathogenesis of syringomyelia (SM), a neurological pathology characterized by the formation of a cystic cavity (syrinx) in the center of the spinal cord (SC), has not yet been given. The SM pathology forms a coaxial elastic tube system with the inner tube formed by the spinal cord having a syrinx and the outer tube formed by the spinal column (dura and vertebrae). It has been assumed that abnormal cerebrospinal fluid (CSF) pressure caused by subarachnoid space (SAS) flow blockage (stenosis) is the underlying cause of syrinx formation and subsequent pain in the patient, but paucity in detailed in vivo pressure data have made theoretical explanation for the syrinx difficult. In order to understand this complex pressure environment, four in vitro models representative of various conditions associated with SM were examined. Overall, interaction of the syrinx and stenosis resulted in a diastolic valve mechanism which could have the effect of syrinx enlargement. In all experiments, the blockage was shown to increase and dissociate SAS pressure, while longitudinal pressure in the syrinx remained largely unchanged. These results provide data for validation of computational models and existing SM theories.

Bioprinted Nanoparticles for Tissue Engineering Applications

2009 ◽  
Author(s):  
Kivilcim Buyukhatipoglu ◽  
Robert Chang ◽  
Wei Sun ◽  
Alisa Morss Clyne
Keyword(s):  
Tissue Engineering ◽  
Tissue Growth ◽  
Bioactive Components ◽  
Engineering Applications ◽  
Tissue Properties ◽  
Native Tissue ◽  
3D Architecture

Tissue engineering may require precise patterning of cells and bioactive components to recreate the complex, 3D architecture of native tissue. However, it is difficult to image and track cells and bioactive factors once they are incorporated into the tissue engineered construct. These bioactive factors and cells may also need to be moved during tissue growth in vitro or after implantation in vivo to achieve the desired tissue properties, or they may need to be removed entirely prior to implantation for biosafety concerns.

Current trends in mathematical modeling of tumor–microenvironment interactions: a survey of tools and applications

2010 ◽  
Vol 235 (4) ◽  
pp. 411-423 ◽  
Author(s):  
Katarzyna A Rejniak ◽  
Lisa J McCawley
Keyword(s):  
Mathematical Modeling ◽  
Protein Interactions ◽  
Computational Models ◽  
Chemical Species ◽  
Tumor Stroma ◽  
Cellular Functions ◽  
Complex Interactions ◽  
Expanding Population

In its simplest description, a tumor is comprised of an expanding population of transformed cells supported by a surrounding microenvironment termed the tumor stroma. The tumor microcroenvironment has a very complex composition, including multiple types of stromal cells, a dense network of various extracellular matrix (ECM) fibers interpenetrated by the interstitial fluid and gradients of several chemical species that either are dissolved in the fluid or are bound to the ECM structure. In order to study experimentally such complex interactions between multiple players, cancer is dissected and considered at different scales of complexity, such as protein interactions, biochemical pathways, cellular functions or whole organism studies. However, the integration of information acquired from these studies into a common description is as difficult as the disease itself. Computational models of cancer can provide cancer researchers with invaluable tools that are capable of integrating the complexity into organizing principles as well as suggesting testable hypotheses. We will focus in this Minireview on mathematical models in which the whole cell is a main modeling unit. We will present a current stage of such cell-focused mathematical modeling incorporating different stromal components and their interactions with growing tumors, and discuss what modeling approaches can be undertaken to complement the in vivo and in vitro experimentation.

In-vivo and In-vitro Evidence of a Carrier-mediated Efflux Transport System for Oestrone-3-sulphate across the Blood-Cerebrospinal Fluid Barrier

2000 ◽  
Vol 52 (3) ◽  
pp. 281-288 ◽  
Author(s):  
TAKEO KITAZAWA ◽  
KEN-ICHI HOSOYA ◽  
TAKEO TAKAHASHI ◽  
YUICHI SUGIYAMA ◽  
TETSUYA TERASAKI
Keyword(s):  
Cerebrospinal Fluid ◽  
Transport System ◽  
Efflux Transport

Electrophysiological characterization and computational models of HVC neurons in the zebra finch

2013 ◽  
Vol 110 (5) ◽  
pp. 1227-1245 ◽  
Author(s):  
Arij Daou ◽  
Matthew T. Ross ◽  
Frank Johnson ◽  
Richard L. Hyson ◽  
Richard Bertram
Keyword(s):  
Computational Models ◽  
Premotor Cortex ◽  
Brain Slices ◽  
Ionic Currents ◽  
Proper Name ◽  
Using Data ◽  
Electrophysiological Characterization

The nucleus HVC (proper name) within the avian analog of mammal premotor cortex produces stereotyped instructions through the motor pathway leading to precise, learned vocalization by songbirds. Electrophysiological characterization of component HVC neurons is an important requirement in building a model to understand HVC function. The HVC contains three neural populations: neurons that project to the RA (robust nucleus of arcopallium), neurons that project to Area X (of the avian basal ganglia), and interneurons. These three populations are interconnected with specific patterns of excitatory and inhibitory connectivity, and they fire with characteristic patterns both in vivo and in vitro. We performed whole cell current-clamp recordings on HVC neurons within brain slices to examine their intrinsic firing properties and determine which ionic currents are responsible for their characteristic firing patterns. We also developed conductance-based models for the different neurons and calibrated the models using data from our brain slice work. These models were then used to generate predictions about the makeup of the ionic currents that are responsible for the different responses to stimuli. These predictions were then tested and verified in the slice using pharmacological manipulations. The model and the slice work highlight roles of a hyperpolarization-activated inward current ( Ih), a low-threshold T-type Ca2+ current ( ICa-T), an A-type K+ current ( IA), a Ca2+-activated K+ current ( ISK), and a Na+-dependent K+ current ( IKNa) in driving the characteristic neural patterns observed in the three HVC neuronal populations. The result is an improved characterization of the HVC neurons responsible for song production in the songbird.

scholarly journals Mending a broken heart: In vitro, in vivo and in silico models of congenital heart disease

2021 ◽  
Vol 14 (3) ◽  
pp. dmm047522
Author(s):  
Abdul Jalil Rufaihah ◽  
Ching Kit Chen ◽  
Choon Hwai Yap ◽  
Citra N. Z. Mattar
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Computational Models ◽  
Developing Heart ◽  
Heterogenous Group ◽  
In Silico Models ◽  
Large Animals

ABSTRACTBirth defects contribute to ∼0.3% of global infant mortality in the first month of life, and congenital heart disease (CHD) is the most common birth defect among newborns worldwide. Despite the significant impact on human health, most treatments available for this heterogenous group of disorders are palliative at best. For this reason, the complex process of cardiogenesis, governed by multiple interlinked and dose-dependent pathways, is well investigated. Tissue, animal and, more recently, computerized models of the developing heart have facilitated important discoveries that are helping us to understand the genetic, epigenetic and mechanobiological contributors to CHD aetiology. In this Review, we discuss the strengths and limitations of different models of normal and abnormal cardiogenesis, ranging from single-cell systems and 3D cardiac organoids, to small and large animals and organ-level computational models. These investigative tools have revealed a diversity of pathogenic mechanisms that contribute to CHD, including genetic pathways, epigenetic regulators and shear wall stresses, paving the way for new strategies for screening and non-surgical treatment of CHD. As we discuss in this Review, one of the most-valuable advances in recent years has been the creation of highly personalized platforms with which to study individual diseases in clinically relevant settings.

scholarly journals Cerebrospinal Fluid Pulsation Stress Promotes the Angiogenesis of Tissue-Engineered Laminae

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Linli Li ◽  
Yiqun He ◽  
Han Tang ◽  
Wei Mao ◽  
Haofei Ni ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cerebrospinal Fluid ◽  
Engineering Technology ◽  
Expression Levels ◽  
Fluid Pulsation ◽  
Endothelial Growth Factor ◽  
The Impact

Background. Angiogenesis is a prerequisite step to achieve the success of bone regeneration by tissue engineering technology. Previous studies have shown the role of cerebrospinal fluid pulsation (CSFP) stress in the reconstruction of tissue-engineered laminae. In this study, we investigated the role of CSFP stress in the angiogenesis of tissue-engineered laminae. Methods. For the in vitro study, a CSFP bioreactor was used to investigate the impact of CSFP stress on the osteogenic mesenchymal stem cells (MSCs). For the in vivo study, forty-eight New Zealand rabbits were randomly divided into the CSFP group and the Non-CSFP group. Tissue-engineered laminae (TEL) was made by hydroxyapatite-collagen I scaffold and osteogenic MSCs and then implanted into the lamina defect in the two groups. The angiogenic and osteogenic abilities of newborn laminae were examined with histological staining, qRT-PCR, and radiological analysis. Results. The in vitro study showed that CSFP stress could promote the vascular endothelial growth factor A (VEGF-A) expression levels of osteogenic MSCs. In the animal study, the expression levels of angiogenic markers in the CSFP group were higher than those in the Non-CSFP group; moreover, in the CSFP group, their expression levels on the dura mater surface, which are closer to the CSFP stress stimulation, were also higher than those on the paraspinal muscle surface. The expression levels of osteogenic markers in the CSFP group were also higher than those in the Non-CSFP group. Conclusion. CSFP stress could promote the angiogenic ability of osteogenic MSCs and thus promote the angiogenesis of tissue-engineered laminae. The pretreatment of osteogenic MSC with a CSFP bioreactor may have important implications for vertebral lamina reconstruction with a tissue engineering technique.

scholarly journals Clearance of cerebrospinal fluid from the sacral spine through lymphatic vessels

2019 ◽  
Vol 216 (11) ◽  
pp. 2492-2502 ◽  
Author(s):  
Qiaoli Ma ◽  
Yann Decker ◽  
Andreas Müller ◽  
Benjamin V. Ineichen ◽  
Steven T. Proulx
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Space ◽  
Near Infrared ◽  
Cranial Nerves ◽  
Lymphatic Vessels ◽  
Intraventricular Injection ◽  
Spinal Subarachnoid Space ◽  
Cord Injury ◽  
Sacral Spine

The pathways of circulation and clearance of cerebrospinal fluid (CSF) in the spine have yet to be elucidated. We have recently shown with dynamic in vivo imaging that routes of outflow of CSF in mice occur along cranial nerves to extracranial lymphatic vessels. Here, we use near-infrared and magnetic resonance imaging to demonstrate the flow of CSF tracers within the spinal column and reveal the major spinal pathways for outflow to lymphatic vessels in mice. We found that after intraventricular injection, a spread of CSF tracers occurs within both the central canal and the spinal subarachnoid space toward the caudal end of the spine. Outflow of CSF tracers from the spinal subarachnoid space occurred predominantly from intravertebral regions of the sacral spine to lymphatic vessels, leading to sacral and iliac LNs. Clearance of CSF from the spine to lymphatic vessels may have significance for many conditions, including multiple sclerosis and spinal cord injury.

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