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1
Altas, Melanie. "Spinal cord transplants in a rat model of spinal cord injury." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0021/MQ49305.pdf.
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Bhatnagar, Timothy. "Quantification of morphological changes of the cervical spinal cord during traumatic spinal cord injury in a rodent model." Thesis, University of British Columbia, 2015. http://hdl.handle.net/2429/52175.
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Traumatic spinal cord injury initiates a complex pathophysiological process that eventually manifests as persistent tissue damage and possible permanent loss of neurologic function. Current experimental models are limited to measuring the gross mechanical response of the spinal cord during injury; thus, little is known about how the internal tissues of the spinal cord deform during injury. The general aims of this research were to develop a method to observe the internal deformations of the in vivo rat spinal cord during clinically-relevant injury models and to determine if the patterns of deformation were correlated to tissue damage manifesting after the injury. To facilitate this work, a novel apparatus and a number of novel methods were developed. First, an apparatus that was capable of inducing contusion and dislocation spinal cord injuries in an in vivo rat model, inside of an MR scanner, was developed. The reported contusion and dislocation injury speeds were comparable with existing spinal cord injury devices, and contusion injury magnitudes showed good accuracy and precision. The device facilitated direct observation and differentiation of the morphological change of the spinal cord tissues during injury. The three-dimensional tissue motion was quantified using a state-of-the-art deformable image registration algorithm that produced displacement fields throughout the volume of the spinal cord around the site of the injury. Furthermore, the image registration methods were validated against a gold-standard. The displacement fields were used to generate transverse-plane mechanical finite strain fields in the spinal cord and the contusion and dislocation injury mechanisms produced distinctly different patterns of tissue deformation in the spinal cord. Lastly, the relationship between mechanical strain and the ensuing tissue damage was investigated in the ventral horns of the gray matter of the spinal cord. This work suggests that compressive strain contributes to the tissue damage in the ventral horns of the gray matter. However, the most important conclusion from this work is that internal observation of the spinal cord tissue during injury provides an invaluable experimental data set that can be used to improve our understanding of the relationship between deformation during injury and manifestation of damage.Applied Science, Faculty of
Mechanical Engineering, Department of
Graduate
3
Fukuda, Seijun. "New canine spinal cord injury model free from laminectomy." Kyoto University, 2006. http://hdl.handle.net/2433/135626.
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Lucas, Erin. "Measuring in vivo internal spinal cord deformations during experimental spinal cord injury using a rat model, radiography, and fiducial markers." Thesis, University of British Columbia, 2010. http://hdl.handle.net/2429/27808.
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Spinal cord injuries (SCIs) are commonly studied experimentally by causing injury to rodent spinal cords in vivo and analyzing behavioral and histological results post injury. Few researchers have directly investigated the deformation of the in vivo spinal cord during impact, which is thought to be a predictor of injury. This knowledge would help to establish correlations among impact parameters, internal structure deformation, and histological and functional outcomes. The objective of this thesis was to develop a radiographic method of tracking the real-time internal deformations of an anesthetized rat‘s spinal cord during a typical experimental SCI.
A technique was developed for injecting fiducial markers into the dorsal and ventral white and grey matter of in vivo rat spinal cords. Two radio-opaque beads were injected into C5/6 in the approximate location of the dorsal and ventral white matter. Four additional beads were glued to the surface of the cord caudal and cranial to the injection site (one dorsal, one ventral). Overall bead displacement was measured during quasi-static compression using standard medical x-ray equipment. Dynamic bead displacement was tracked during a dorsal impact (130mm/s, 1mm depth) by imaging laterally at 3,000 fps using a custom high-speed x-ray system.
The internal spinal cord beads displaced 1.02-1.7 times more than the surface beads in the cranial direction and 2.5-11 times more in the ventral direction for the dynamic impact and maximum quasi-static compressions. The dorsal spinal cord beads (internal and surface) displaced more than the ventral spinal cord beads during all compressions. Finite element modeling and experimental measurements suggested that bead migration with respect to the spinal cord tissue was small and mostly insignificant.
These results support the merit of this technique for measuring in vivo spinal cord deformation. The differences in bead displacements imply that the spinal cord undergoes complex internal and surface deformations during impact. Many applications of this technique are conceivable including validating finite element and surrogate models of the spinal cord, comparing localized grey and white matter motion during impact to histological findings, and improving SCI preventative and treatment measures.
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Prince, Karen. "The computational modelling of the spinal cord neurons involved in the pain process." Thesis, University of Northampton, 2006. http://nectar.northampton.ac.uk/2696/.
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Pain is a personal subjective experience with physiological and psychological components and involves many complex processes. In 1965 Melzack and Wall proposed the influential gate control theory (GCT) of pain and, in general, this has been supported by subsequent research. This theory postulates that cells in the substantia gelatinosa, located within the spinal cord, act like a gate mechanism that modulates the flow of information through the spinal cord to the brain and thus impacts on the pain experience. The abundance of literature and experimental data that is available from pain research supports the development and testing of computational models for the simulation and exploration of the pain process. Despite the fact that pain is an ideal candidate for modeling, it is an area that has received little attention. One of the few published models (Britton and Skevington, 1989; Britton et al., 1996) translated the explicitness of the GCT and its well-defined architecture into a basic mathematical model. The aim of this research is to develop a biologically appropriate computational model of pain, capable of modelling both acute and chronic pain states, and describe applications and simulations appropriate to such a model. Therefore this research firstly replicates a mathematical model of pain (Britton and Skevington, 1989; Britton et al., 1996) to explore its adequacy and to assess its potential for further development. The original model is then developed and extended to produce a more biologically plausible representation of the pain processes involved in the Gate Control mechanism. The improvements in the computational model have enabled a clinically plausible simulation of a pain modulatory technique, transcutaneous electrical nerve stimulation (TENS), which validates the model’s representation of the GCT and provides insight into how pain modulation can occur. Other developments to this model show its unique ability to represent symptoms of chronic pain, such as allodynia and hyperalgesia, which are associated with pathological pain states developed through the loss of inhibition and glial cell activation
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Sowd, Matthew Michael. "Analyzing Non-Unique Parameters in a Cat Spinal Cord Motoneuron Model." Thesis, Georgia Institute of Technology, 2006. http://hdl.handle.net/1853/11545.
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When modeling a neuron, modelers often focus on the values of parameters that produce a desired output. However, if these parameters are not unique, there could be a number of parameter sets that produce the same output. Thus, even though the values of the various maximum conductances, half activation voltages and so on differ, as a set they can produce the same spike height, firing rates, and so forth.
To examine whether or not parameter sets are unique, a 3-compartment motoneuron model was created that has 15 target outputs and 59 parameters. Using parameter searches, over one hundred parameter sets were created for this model that produced the same output (within tolerances). Parameter values vary between parameter sets and indicate that the parameter values are not unique. In addition, some parameters are more tightly constrained than others. Principal component analysis is used to examine the dimensionality of the input and output spaces.
However, neurons are more than static output generators. For example, a variety of neuromodulatory influences are known to shift parameter values to alter neuronal output. Thus the question arises as to whether this non-uniqueness extends from model outputs to the models sensitivities to its parameters. In this work, the non-unique parameter sets are further analyzed using sensitivity analyses and output correlations to show that these values vary significantly between these parameter sets. Therefore, each of these models will react to parameter variation differently.
This work concludes that parameter sets are non-unique but have varying sensitivity analyses and output correlations. The ramifications of this are discussed for both modelers and neuroscientists.
7
Rogers, A. T. "Spinal cord cell culture : a model for neuronal development and disease." Thesis, University of Bath, 1988. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.234048.
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Chen, Hsiao-Yu. "Developing a model of spinal cord injury rehabilitation nursing using grounded theory." Thesis, University of Ulster, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.413285.
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Corkill, Dominic John. "Endothelin-1 induced focal ischaemia : a novel model of spinal cord injury." Thesis, University of Southampton, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.397757.
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Goode, Stephen Thomas. "Development of a spinal cord injury model using the material point method." Thesis, University of Leeds, 2016. http://etheses.whiterose.ac.uk/17561/.
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Spinal cord injury (SCI) is characterised by permanent loss of motor and sensory function. The primary damage from the initial mechanical insult is exacerbated by the secondary patho-physiological cascade. Research into neuroprotective interventions to preserve tissue and reduce the damage caused by the secondary injury is hampered, in part, due to a lack of understanding of the link between the biomechanics of the primary traumatic injury and the subsequent evolution of the secondary injury. Hence, there is a need to better understand the biomechanics of SCI, the distinct injury patterns produced, and how these affect the evolution of the secondary cascade. Computational models using finite element methods (FEM) have been established as a useful tool for investigating SCI biomechanics. These may be used to obtain data that is difficult or impossible to capture through in vivo and in vitro experiments, in particular; stress and strain fields within the neural tissue. However, the complexity of these models is limited by difficulties. These include: problems coping with large deformations over short periods of time due to mesh tangling, difficulties in incorporating the fluid structure interactions, and scalability issues when attempting to make use of high performance computing facilities, utilising large numbers of processors. This work has involved the creation of a computational spinal cord injury using the Material Point Method (MPM) and MPMICE (MPM for Implicit, Continuous Fluid, Eulerian), alternative computational methods that overcome these limitations. The model incorporates the neural spinal cord tissue, the dura mater, and the cerebrospinal fluid. This model has been validated against equivalent experimental and FEM results. MPM/MPMICE was found to be a viable alternative to FEM for modelling SCI computationally, with the potential to enable more complex and anatomically detailed models through the utilisation of increased parallel computation.
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Mattucci, Stephen Frank Ernesto. "A biomechanical investigation of a dislocation spinal cord injury in a rat model." Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/64175.
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Traumatic spinal cord injuries clinically occur in a heterogeneous fashion, including at different spinal levels, injury velocities, and injury mechanisms. Clinical treatment options, such as early surgical decompression produce inconsistent recovery outcomes in the patient population, despite demonstrating effectiveness in preclinical animal models. The most common biomechanical factors, such as cervical level, high-energy impact and dislocation injury mechanism, are not adequately represented in preclinical models, which may explain the lack of agreement between clinical studies. The overall objective of this thesis was to investigate the biomechanics of a high-speed cervical dislocation rat model at acute stages, refine the model, and incorporate residual compression. The temporal progression of acute SCI was investigated in different injury mechanisms, where dislocation injuries demonstrated the fastest loss of white matter tissue. To refine the dislocation model, new vertebral injury clamps were designed with a feature allowing the clamps to pivot and self-align when tightened. The vertebral kinematics during a dislocation injury were analysed using high-speed x-ray and clamp slippage was significantly reduced with the self-aligning clamps, compared to the existing clamps. This study also emphasized the importance of validating injury displacements against input parameters, particularly when comparing results or reproducing injuries. In order to implement residual compression within the dislocation model, injury parameters were independently investigated. Electrophysiology techniques were implemented to determine a minimum residual compression depth that affects signal conduction following a traumatic injury. Continuously holding the residual compression following the initial injury induced a significantly different physiological response compared to when the injury was immediately reduced. Behavioural outcome was used to identify severities following a range of displacements, and four hours of residual compression was survivable following a ‘mild’ traumatic injury, indicating suitable parameters for future studies. Rats of the same weight were identified to have different anatomical dimensions and structural properties of the spinal column, potentially influencing injury outcomes in closed-column models. The continued development and implementation of the cervical dislocation injury model in the rat will deepen understanding of SCI biomechanics and provide an additional clinically-relevant injury model for testing the robustness of potential treatment therapies.Applied Science, Faculty of
Graduate
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Ross, Lewis. "The development of an in vitro model of spinal cord injury using microfabrication." Thesis, University of Glasgow, 2013. http://theses.gla.ac.uk/4365/.
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This project aimed to develop an in vitro model of spinal cord injury. A device was developed that could, in conjunction with an existing myelinating culture system, aligned axons into parallel rows and contain the soma to a predefined area; thus creating a structure similar to the spinal cord. It was intended for the device to be simple to produce and use, provide easy accesses to the axons for wounding and allow simple measurement of axonal regrowth. An additional aim of the project was to develop a method of cell wounding that was reproducible, precise and allowed observation of the wounding process. A series of ridges were created on PDMS devices, which were used to align the axons. These ridges were 5 μm deep and 12.5, 25 or 50 μm wide. The 12.5 μm ridges aligned an average of 54% of the axons within 10° of the axis parallel to the ridges. The 25 and 50 μm only managed to align 37% and 28% in this direction. Flat control devices aligned 16% of the axons in an equivalent direction, which corresponded to a random alignment. From this it was concluded that 12.5 μm ridges should be used to align the axons. Rows of 25 μm high, 20 μm diameter pillars were placed across the devices in an attempt to contain cells to one side of the device. The pillars had gaps between them of 6, 8 or 10 μm. MG63 cells were used to test the pillars’ containment ability. It was found that the cells could climb over the pillars and so multiple rows of pillars where created to attempt to trap the cells. The multiple rows did not full contain the cells but it was found that 5 rows with gaps sizes of 6 μm could slow the cells migration across the devices. It was found that the pillar rows were not necessary to contain the neuronal soma, as they would not migrate far from their initial seeding area. However, the pillars had an effect on the axons’ alignment. One, three and five rows of pillars reduced the alignment to 40%, 24% and 28% respectively. It was hypothesised that the axons were using the pillars as a “turning post”. An automated method of wounding the cells was developed using a microscope and micromanipulator. This method was trialled on layers of astrocytes and MG63s grown on flat and grooved PDMS. Cutting astrocytes perpendicular to the grooves resulted in wounds with an area five times larger than those caused by cutting parallel to the grooves. Perpendicular wounds were also twice the area of those on flat PDMS. Similar effects were seen on MG63s. It was hypothesised that the difference in wounds sizes was due to the ridges causing the cells to make stronger mechanical connections longitudinally with the grooves.
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Jones, Page. "Enzymatic and proteomic analysis of spinal cord in a G93A ALS mouse model." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2008. https://www.mhsl.uab.edu/dt/2008r/jonesp.pdf.
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Otoshi, Chad Kuniyuki. "Receptor plasticity in the lumbar spinal cord a move to a simpler model /." Diss., Restricted to subscribing institutions, 2008. http://proquest.umi.com/pqdweb?did=1679374141&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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Merta, Nika Janet. "A spinal cord model for studying diffusion and enhanced mixing of a dye." [Gainesville, Fla.] : University of Florida, 2009. http://purl.fcla.edu/fcla/etd/UFE0025071.
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Gensel, John Carib. "Modeling and treatment of rat cervical spinal cord injury." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1167753874.
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Marchionne, Francesca. "INTRATHECAL DELIVERY OF BDNF TO THE LUMBAR SPINAL CORD VIA IMPLANTED MINI-PUMP RESTORES STEPPING AND MODULATES THE ACTIVITY OF THE LUMBAR SPINAL INTERNEURONS IN A LARGE ANIMAL MODEL OF SPINAL CORD INJURY." Diss., Temple University Libraries, 2017. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/480625.
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BioengineeringPh.D.
Delivery of neurotrophins to the injury site via cellular transplants or viral vectors administration has previously been shown to promote recovery of locomotor behavior in the absence of locomotor training in adult spinalized animals. Viral vectors still pose clinical concerns associated to recombinant genetics and the lack of understanding of how they react with the human immune system. Delivery via graft of autologous fibroblast engineered to produce brain derived neurotrophic factor (BDNF) and Neurotrophin-3 (NT-3) has been shown as a valuable method; however, the need for multiple invasive surgeries, along with the impossibility of delivering a controlled and constant dosage of protein are serious obstacles to obtaining approval by the FDA. The present study was aimed at evaluating the efficacy of BDNF delivered to the lumbar locomotor centers using a clinically translational delivery method at restoring stepping abilities in a large animal model of spinal cord injury. We wanted to evaluate if intrathecal delivery of BDNF to the lumbar spinal cord would promote a locomotor recovery as effective as delivery to the injury site, even at doses low enough not to trigger the side effects observed at high doses. A programmable and implantable mini-pump was used to intrathecally deliver a 50 ng/day dose of BDNF to the lumbar spinal cord for 35 days after spinal thoracic transection. Kinematic evaluation was conducted before, 3 and 5 weeks after injury/pump implant. Ground reaction forces (GRFs) analysis was performed 5 weeks after injury to evaluate the animals’ ability to weight support during locomotion and standing trials. Results showed that treated cats were capable of executing weight-bearing plantar stepping at all velocities tested (0.3-0.8 m/s). Control cats did not recover stepping ability, especially at higher velocities, and dragged their hind paws on the treadmill. We were also interested in measuring the extent of BDNF diffusion within the lumbar area of the spinal cord and the potential damage to the cord caused by catheter insertion. Immunohistological evaluation showed higher BDNF expression in the dorsal root ganglions, with BDNF Immuno-Histo Chemistry (IHC) extending from L3 to L7 in all treated cats. BDNF was also found within multiple cells of the grey matter, although the levels were not significantly higher than background density. Glial fibrillary acidic protein (GFAP) stain was used to measure the immunohistological reaction of the spinal cord to the implanted catheter, and to establish the safety of the delivery method. Gross examination of the spinal cord post-mortem revealed no damage to the cord or the roots with minimal encapsulation of the catheter/pump. Minimal tissue inflammation was revealed by the GFAP stain, underlying the safety of our method. We also wanted to investigate and characterize changes in the locomotor circuitry induced by BDNF delivery. Comparison of multiunit activity in the lumbar area between BDNF treated and non-treated cats allows a better understanding of the mechanism of action of BDNF on the spinal interneurons. This was accomplished by extracellularly recording lumbar interneuronal firing during air-stepping in a 5 weeks post-injury terminal experiment. The cord was exposed at the lumbar level between the L3 and L7 spinal segments. In-vivo recordings of spinal extracellular signals were conducted using two 64 channels microelectrode arrays inserted at the dorsal root entry zone to depths of ~3000µm and ~1500µm. The ability to record simultaneous activity of multiple single neurons made it possible to study the extent to which spiking activity in a given neuron is related to concurrent ensemble spiking activity. A point process generalized linear model (PP-GLM) approach was used to assess the strength of the connections between spike trains. Interneurons activity was assessed in terms of average firing rate, signal-to-noise ratio (SNR), and number of active units per trial. Although BDNF infusion in the lumbar segments did not show significant effect on strengthening synaptic connections, we did find greater multiunit activity in the treated animals, sign of a potential BDNF-induced increase in interneuronal activation, which could be likely involved in recovery of stepping ability after SCI. Together, findings from these aims demonstrated the therapeutic potential of intrathecal lumbar BDNF delivery in spinalized animals. Constant infusion of BDNF to the locomotor centers promotes locomotor recovery similar to training or delivery to the injury site via cellular transplants after complete SCI. Intrathecal delivery by an implantable/programmable pump is a safe and effective method for delivery of a controlled BDNF dosage; it poses minimal risks to the cord and is clinically usable. Lastly, this study confirmed the major involvement of BDNF in increasing the activity of the interneurons in the locomotor circuitry, opening the door to further investigating the mechanism through which neurotrophins induce recovery of locomotion.
Temple University--Theses
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Almarestani, Lina. "Changes in the spinal cord and peripheral innervation in an animal model of arthritis." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=32288.
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Neurons in the marginal layer (lamina I) of the dorsal horn of the spinal cord play a major role in the transmission and integration of pain-related sensory information that is relayed to the brain. Alteration in excitability of these cells greatly influences pain perception. Among these, alterations of the substance P (SP) system play a major role because of its known involvement in spinal cord nociceptive mechanisms. In this thesis, our main focus was on the characterization of the cell populations in lamina I of the spinal cord which express the SP receptor (NK-1r) and project to the parabrachial nucleus in normal rats and in an animal model of localized polyarthritis. Lamina I projection neurons can be classified into three morphological types, the fusiform, the multipolar (flattened) and the pyramidal. Our combined tract-tracing and immunocytochemical studies demonstrated that in control animals the fusiform and multipolar neurons project abundantly to the parabrachial nuclei and express the NK-1r, whereas pyramidal neurons, although projecting in almost identical proportion to the same target, express little, if any, NK-1r. In rats treated with a single, unilateral low dose subcutaneous injection of complete Freund's adjuvant (CFA) in the thick skin of the hind paw, we demonstrated an ipsilateral de novo NK-1r expression on the normally non-nociceptive spinoparabrachial lamina I pyramidal cell type starting at 15 days post-injection. We also observed, as from 15 days post-CFA, an innervation of pyramidal neurons by SP-immunoreactive (IR) boutons. It should be pointed out that pyramidal neurons are normally not innervated by SP, which would confirm their non-nocicDans la moelle épinière, les neurones de la couche marginale (couche 1) de la corne dorsale jouent un rôle majeur dans l'intégration et la transmission de l'information sensorielle vers le cerveau. Des changements au niveau de l'excitabilité de ces cellules influencent grandement la perception de la douleur. Parmi ceux-ci, un changement au niveau du système de la substance P (SP) peut avoir un grand impact en raison de son implication dans les mécanismes nociceptifs. Dans cette thèse, notre but premier était de caractériser la population neuronale de la couche 1 qui exprime le récepteur de la substance P (NK-1 et qui projette au noyau parabrachial. Les observations se sont faites chez les rats normaux et dans un modèle animal de polyarthrite locale. Les cellules de projection de la couche 1 peuvent être classifiées en trois types morphologiques; les fusiformes, les multipolaires (aplaties) et les pyramidales. Notre approche combinant le traçage rétrograde et l'immunocytochimie a démontré que, chez les animaux contrôles, les neurones fusiformes, multipolaires et pyramidaux projettent abondamment au noyau parabrachial. Les deux premiers types de cellules expriment le récepteur NK-1, alors que les cellules pyramidales l'expriment très peu, sinon pas. Chez les rats traités avec une seule dose unilatérale d'adjuvant complet de Freund (ACF), administrée sous-cutanée dans la plante de la patte, nous avons démontré une nouvelle expression du récepteur NK-1. Les cellules pyramidales qui sont habituellement non nociceptives sont imunoréactives pour le récepteur NK-1 à partir de 15 jours après l'injection. Nous avons aussi observé, à 15 jours apr
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Szebeni, Katalin, Attila Szebeni, T. DiPeri, N. Davis, Gregory A. Ordway, and J. L. Ardell. "Thoracic Spinal Cord Stimulation Protects the Hippocampus in a Canine Model of Heart Failure." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etsu-works/8635.
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Scali, Manuela. "Fluoxetine treatment promotes functional recovery in a rat model of cervical spinal cord injury." Doctoral thesis, Scuola Normale Superiore, 2014. http://hdl.handle.net/11384/85978.
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Cocchi, M. A. "THE MELATONIN PROTECTIVE ROLE IN AN ORGANOTYPIC MODEL OF SPINAL CORD INJURY SECONDARY DAMAGE." Doctoral thesis, Università degli Studi di Milano, 2016. http://hdl.handle.net/2434/351674.
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Spinal cord injury (SCI) is characterized to be a two-step process composed by the primary lesion consisting of the initial trauma and the secondary damage, characterized by multiple processes including inflammation, oxidative stress and cell death that lead to a significant expansion of the original damage and to an increase of the functional deficit. Among the aforementioned processes, the oxidative stress plays a significant role in pathophysiology of SCI. In this study, we evaluated the role of melatonin, potent antioxidant and immunomodulator indoleamin, on the oxidative stress, the tissue viability and the neuritic plasticity deriving from the gray matter in an experimental model of organotypic cultures. These cultures consisted of Sprague Dawley rat spinal cord slice treated with hydrogen peroxide (H2O2). In five experimental groups, A) Control Group (CTR) – Organotypic spinal cord slice culture (350μm); B) Stressed Group (H2O2) – Organotypic spinal cord slice culture (350μm) exposed to H2O2 (50 μM); C) Control Group treated with melatonin (10-5M) of 24 hours (CTR+MEL) – Organotypic spinal cord slice culture (350μm) treated with melatonin for 24 hours; D) Treated Group (H2O2+MEL-POST) – Organotypic spinal cord slice culture (350μm) exposed to H2O2 (50 μM) and treated after 24 hours with melatonin (10-5M) for 24 hours; E) Treated Group (H2O2+MEL-PRE) – Organotypic spinal cord slice culture (350μm) pre-treated with melatonin (10-5M) for 24 hours (50 μM) and exposed to H2O2 for other 24 hours.
We investigated the slice cellular death by propidium iodide (PI) assay, the slice vitality by MTT assay, the superoxide dismutase (SOD) and total thiols (SH) levels for the contrast to the oxidative stress, the neuronal (NeuN) and the synaptophysin (Syp) immunopositivity. Melatonin significantly decreased the number of dead cells, increased slice vitality, mainly in slices treated before H2O2 exposition. Melatonin enhanced SOD immunopositivity, contrasted total thiols decrease, attenuated Syp reduction and increased NeuN immunopositivity. Overall, these findings suggest that melatonin may exert a potentially beneficial effect upon the progression of SCI secondary damage, protecting the tissue from a further degeneration.
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Chen, Henry Szu-Meng. "Validation and optimization of myelin water imaging in a preclinical model of spinal cord injury." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/59685.
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Myelin content is an important marker for neuropathology; however, direct imaging of myelin is difficult. Consequently, quantitative T2 based myelin water imaging measures myelin content indirectly by probing the property of the surrounding water. Typically, a lengthy multi-echo spin-echo sequence is used to obtain decay curves that are fitted to produce T2 distributions. In white matter, two peaks are observed, one with short and one with long T2 associated with water trapped between the myelin lipid bilayers and intra/extracellular water. The ratio of myelin water peak to the entire distribution is called the myelin water fraction (MWF) and correlates well the myelin content.
This thesis has two parts. The first half deals with the use of compressed sensing (CS) to accelerate the lengthy sequence used in myelin water imaging. The CS CPMG sequence was implemented in 2D utilizing group-sparse reconstruction in order to take advantage of the correlation between echoes. Simulated undersampling and real undersampling experiments were performed. It was found that acceleration up to 2× was possible without impacting MWF map quality, wherever adequate SNR was available. This is followed by a brief investigation into 3D CS CPMG, where similar results were achieved.
The second part of the thesis focuses on myelin water imaging in the presence of myelin debris. Because MWF is associated with the water trapped in between the myelin lipid bilayers, the reading depends heavily on myelin morphology. I compared MWF to transmission electron microscopy (TEM) derived myelin fraction using a rat injury model at normal (normal myelin), 3 weeks post-injury (a large amount of myelin debris), and 8 weeks post-injury (myelin debris partially cleared). I found that myelin water fraction correlated strongly with the amount of myelin lipid bilayers in both intact myelin and myelin debris. From the TEM images, it appears that myelin debris consists of areas of either normally spaced myelin or large watery spaces. No significant difference was found in myelin period among the three groups.Science, Faculty of
Physics and Astronomy, Department of
Graduate
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Joshi, Mital. "Development and characterization of a graded, in vivo, compressive, murine model of spinal cord injury." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0017/MQ54138.pdf.
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Uzel, Sébastien G. M. "Microfluidic and optogenetic technologies to model spinal cord development and neuromuscular junction formation and function." Thesis, Massachusetts Institute of Technology, 2015. http://hdl.handle.net/1721.1/103850.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2015."June 2015." Cataloged from PDF version of thesis.
Includes bibliographical references (pages 106-118).
Motor neurons located in the spinal cord and innervating muscle cells throughout the body are responsible for virtually all motor functions, from locomotion to respiration or speech. They arise from differentiation of progenitor cells within the neural tube under spatiotemporally well-defined morphogen concentration profiles, and extend axons into the peripheral nervous system following a precisely orchestrated sequence of events involving secreted chemo-attractants and repellents and dynamic expression of the corresponding ligand receptors. Finally, they form neuromuscular junctions, the synapses that transmit electrical signals to the muscle effectors. Failure for these motor neurons to develop or function properly, caused by developmental or neurodegenerative genetic disorders, or as a result of traumatic injuries, lead to highly incapacitating or even lethal malformation and conditions. Microfabricated platforms and optogenetic technologies have proven to be valuable tools to control the microenvironment, biochemical cues and the stimulation applied to neuronal tissues. Precise control of the geometry of microfluidic devices together with their ability to host 3D cell culture has enhanced the physiological relevance of such neuronal tissues relative to traditional 2D culture assays. And the ability to selectively excite neuronal cells with light has opened tremendous opportunities in the field of neuroscience. In this thesis, we combine these two technologies to stimulate and subject cells to chemical and physical microenvironments that emulate their in vivo counterpart. First, we present a microfluidic platform that generates orthogonal concentration gradients and emulates the confined appearance of motor neurons within the developing spinal cord. Then, we introduce a new device capable of forming a 3D compartmentalized neuron-muscle coculture and demonstrate remote stimulation of the myofibers by the motor neurons resulting in muscle contraction. By targeting the stem cells from which the motor neurons are derived with the light sensitive ion channel Channelrhodopsin, we form, in this microfluidic device, the first in vitro light-activatable neuromuscular junction. Keywords: microfluidics, optogenetics, morphogenesis, cell migration, neuromuscular junctions.
by Sébastien G. M. Uzel.
Ph. D.
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Smith, Jenny Thompson. "A 3D culture model to investigate cellular responses to mechanical loading in spinal cord injury." Thesis, University of Leeds, 2016. http://etheses.whiterose.ac.uk/16199/.
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Spinal cord injury (SCI) can cause paralysis, loss of sensation, and respiratory dependency, which has a significant impact on the quality of life of patients, their life expectancy and is also a significant economic burden due to the high costs associated with primary care and loss of income. One of the difficulties in establishing a treatment method is the heterogeneity of SCI; there are many different types and severities of traumatic primary injury, across different age groups of patients and different locations within the spinal cord, whilst at a cellular level, there are multiple, interacting secondary injury cascades that amplify the primary damage inflicted during the traumatic insult. Many techniques have been developed to mimic particular injuries found in human SCI, however in vivo animal models can be extremely costly and time consuming. The modest translation of therapeutic treatments from animal models to successful clinical trials suggests that there is a need for simplified models of SCI, in which the complex secondary cascade can be broken down into specific cellular interactions under controlled injury parameters. It was hypothesised that in vivo injuries could be simulated using a 3D in vitro model of SCI within a tethered, self-aligned, type-I collagen gel. An in vitro model such as this could advance the understanding of cellular responses to injury and help inform animal studies which may facilitate the design of therapeutics. Initially, different matrices were investigated in order to determine their suitability for use as matrix components for a 3D in vitro model of SCI. The matrices were characterised in terms of their mechanical properties, and the cellular responses of astrocytes following culture within the matrices. A fully hydrated matrix was selected which had a lower elastic modulus in comparison to spinal cord tissue, and which maintained astrocytes in a non-reactive state, as determined by the expression of markers for reactive astrogliosis. Contusion models of SCI are thought to generate the most relevant animal models of SCI, therefore their suitability as an injury mechanism within a 3D cellular model was investigated. A pilot study using the Hatteras contusion device, demonstrated that there was potential for in vivo type contusion devices to be utilised with an in vitro 3D collagen gel SCI model. The remainder of the study utilised the Infinite Horizons (IH) in vivo impactor, which is a force controlled contusion device. The experimental parameters utilised with the IH impactor within an in vivo setting were investigated as to their suitability for collagen gel impactions. Following a detailed investigation, the in vivo parameters of an impact force of 200 kdyn and a dwell time of 0 ms, using a 2.5 mm diameter impaction tip were adopted; however the calibration start height of the impaction tip was altered to avoid full penetration of the impactor tip through the gel. The limitations of the contusion device affected the consistency of the impaction and resulted in a lack force output data. These limitations need to be resolved in order to directly compare in vivo and in vitro SCI using the IH impactor. The impaction of 3D aligned, collagen gels, seeded with primary rat astrocytes, using the IH impactor generated a 3D cavity bordered by reactive astrocytes, which was reminiscent of the glial scar and cystic cavity which forms at the lesion site in vivo. An increasing gradient of the astrocyte reactivity marker, glial fibrillary acidic protein, was expressed by cells closest to the impact zone. Astrocytes within the first 100 µm of the impact zone were highly ramified with cellular filaments aligned with the edge of the impact zone. An increase in the expression of astrocyte reactivity markers was observed over a ten-day period following impaction. In summary, a 3D model of SCI was developed that was highly adaptable, and suitable for further advancement to increase the complexity and experimental outputs that were presented in this study. More detailed analysis of the cellular responses, over longer time courses, and perhaps with the additional complexity of multiple cell types would complement investigations within in vivo models. 3D in vitro tethered collagen gel models such as this could provide valuable insights into the cellular mechanisms which may progress the translation of treatments into the clinic.
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Lefeuvre, Jennifer. "Characterization of spinal cord lesions in the marmoset EAE model using MRI and histopathology techniques." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS208.
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Jusqu’à 90% des patients atteints de sclérose en plaque (SEP) présentent des lésions dans la moëlle épinière. L’imagerie par résonance magnétique (IRM) des lésions médullaires demeure un challenge difficile et par conséquent, leur développement et le lien avec la progression clinique du patient restent à ce jour fortement méconnus. Encéphalomyélite auto-immune expérimentale (EAE) chez le marmoset présente des caractéristiques lésionnelles cérébrales ainsi que des déficits sensori-moteurs se rapprochant fortement de la SEP. L’objectif de cette thèse a été de développer de nouveaux protocoles IRM à 7T en association avec des analyses histopathologiques afin de caractériser le type de lésions médullaires et de suivre leur évolution spatio-temporelles chez le marmoset EAE. Notre première étude postmortem nous a permis de démontrer une forte ressemblance des lésions focales avec celles retrouvées chez les patients SEP, ainsi que une grande hétérogénéité des lésions subpiales entre animaux le long de la moelle épinière. Dans un second temps, nous avons mis en place une routine expérimentale robuste adapter à la morphologie de l’animal, ainsi que la création d’une antenne 12-canaux en réseau phasé. Pour la toute première fois, nous avons imager in vivo la totalité de la moëlle épinière de nos primates au cours de la maladie. Nous avons trouvé une forte corrélation entre la charge lésionnelle médullaire et les scores cliniques. Ces nouveaux éléments soulignent la pertinence des lésions médullaires chez le marmoset EAE pour étudier les mécanismes de développement des lésions chez les patients SEPUp to 90% of multiple sclerosis (MS) patients present spinal cord lesions. Magnetic resonance imaging (MRI) of spinal cord lesions is still a difficult challenge. Consequently, the evolution of spinal cord lesions in MS and their contribution to disease progression remain poorly understood. The brain of common marmoset with experimental autoimmune encephalomyelitis (EAE) displays closer radiological and pathological features as well sensori-motor deficits with MS. The objective of this thesis was to develop new MRI protocols at 7 Tesla in association with histopathological analysis to better characterize the type of spinal cord lesions in the marmoset EAE, and to understand their spatiotemporal evolution. A first postmortem study demonstrated a strong resemblance to MS focal lesions in terms of shape and distribution, as well a heterogeneous subpial pathology between animals and along the spinal cord length. Secondly, we implemented a robust in vivo experimental setup in order to adapt to the morphology of the animals and created a 12-element phase-array coil. This new setup enabled us to image for the first time the entire spinal cord of nonhuman primates with EAE during the disease. We also found a strong association between the lesion load and the disability scores. These new findings highlight the relevance of the spinal cord lesions in the marmoset EAE model for studying the disease mechanisms of spinal cord lesions in MS
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Hutchinson, Jessika Marie. "Elimination of microglia from the spinal cord: A model to examine plasticity following peripheral axon injury." Miami University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=miami1533205031089256.
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Lui, R. "IN VIVO IMAGING OF STEM CELL MEDIATED TREATMENT IN A MOUSE MODEL OF SPINAL CORD INJURY." Doctoral thesis, Università degli Studi di Milano, 2010. http://hdl.handle.net/2434/150208.
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Introduction: The use of adult stem cells in cell-mediated therapies is an area of considerable interest within tissue regeneration research. However, important variables such as the distribution of the injected cells, cell survival, target organ localisation cell proliferation and differentiation cannot be evaluated in vivo by using classical imaging approaches. This study propose multiple labelling protocols for in vivo visualisation by MRI, nuclear imaging and BLI of adult murine neural stem cell-mediated therapy, in spinal cord injury animal models. Methods: Murine neural stem cells (mNSCs) were directly labelled with different amounts of SPIOs (0 - 100 - 200 - 400 μg Fe/ml) in the culture medium and incubated with iron labelled medium for 24, 48 or 72 h in presence of carriers such as poly-L-Lysine (PLL), polybrene (PB) and protamine sulphate (PS). PLL and PS were tested at different ratio (Fe/PLL 1:0,03, 1:0,06 and 1:0,09 and Fe/PS 1:0,025 and 1:0,05). Labelled cells were analysed for viability, iron content (Perl’s Staining and spectrophotometer analysis), morphology, staminality and differentiation capability. After the labelling protocol set up, the loaded cells were injected into the tail vein of a spinal cord injury murine model and their distribution was followed by MRI for two months. Initial cell distribution was also followed by nuclear imaging after cell labelling with 111In-oxine (60 μCi/106 cells). Cells localization, distribution e viability, over time, were analysed in vivo by BLI after injection of mNCS infected with a viral vector expressing Luciferase under a PGK constitutive promoter (PLW vector). Results: the iron content/cell increased in proportion to the incubation time and to the iron concentration in the medium and in relation to different carriers (PLL, PB and PS) in labelled mNSCs. Longer incubation time (48 and 72h) and higher iron concentration (400 μg Fe/ml) resulted in marked toxicity and lower cell viability. The use of PB and PLL, as carriers, didn’t produce any increase of the labelling efficiency. The incubation for 24h with 200 μg Fe/ml in presence of different amount of PS didn’t influence significantly the cell viability and the proliferation rate. Furthermore, the percentage of iron-positive cells and the iron content/cell increased in proportion to the PS content in the medium even if higher amount of PS (Fe/PS 1:0.05 ratio) resulted in an aberrant morphology. For this reason, 200 μg Fe/ml incubated with Fe/PS 1:0.025 ratio for 24h, has been chosen as the best labelling condition. Labelled cells were able to form new neurospheres and maintained the nestin expression demonstrating the maintenance of self-renewal capability and stem cell features and were also able to differentiate, as confirmed by β-tubulin III and GFAP expression analysis. Nuclear imaging confirmed initial distribution to filter organs while MRI allowed to detect the presence of an iron signal due to stem cell localization into the lesion site since 7 days after injection. BLI permitted to demonstrate the viability of PLW infected mNSCs migrated at the lesion site and supported the MRI data. Conclusions: These results permitted to conclude that NSCs can be efficiently labelled with different molecules without significantly perturbing physiological stem cell features and self-renewal capability. These labelling protocols can be applied for the in vivo visualisation by MRI, nuclear imaging, and BLI of the distribution of stem cells after their transplantation into murine model of disease.
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Richard, Levine, Richard Vaillancourt, and Ralph Fregosi. "Evaluation of the Brainstem Spinal Cord Preparation in the Neonatal Rat as a Model for Prenatal Nicotine Exposure." The University of Arizona, 2012. http://hdl.handle.net/10150/614504.
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Class of 2012 AbstractSpecific Aims: The goal of this project was to evaluate the use of a preparation of the brainstem and spinal cord of neonatal rats that has been widely used for observing and quantifying central nervous activity, as well as the response to pharmacological manipulation. To achieve this, we specifically aimed to remove the intact brainstem and spinal cord of newborn rats, and develop a preparation that would maintain physiological function and allow for recording of electrical activity. Methods: Multiple dissections were performed on neonatal rats. Conditions during the dissections were controlled to maintain physiological function. Once removed, the intact brainstem and spinal cord was placed in a preparation that allowed for manipulation and access to nerve rootlets. Finally, glass suction electrodes were used to record electrical activity directly from the nerve rootlets. Once recorded, the data were stored on a hard drive for further analysis. Main Results: We were successful in isolating the intact brainstem and spinal cord in neonatal rats while maintaining physiological conditions and nervous activity. The preparation allowed for easy access to nerve roots as well as customization for different experiments. We were also successful in recording nerve activity in the preparation and collection of data for use in future experiments Conclusions: We conclude that the brainstem spinal cord preparation described in this study is a valuable tool that allows for recording and analysis of nerve activity, and specifically for measurement of respiratory motor output. This is a preparation that can be used in a variety of experiments that attempt to observe or quantify the activity of central nerve cells and allows for pharmacological interventions that could be applied in various experiments.
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Ankeny, Daniel P. "The effects of brain-derived neurotrophic factor and intraspinal marrow stromal cell transplantation in a rat model of experimental spinal cord injury." Columbus, Ohio : Ohio State University, 2003. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1040224622.
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Thesis (Ph. D.)--Ohio State University, 2003.Title from first page of PDF file. Document formatted into pages; contains xxiii, 186 p.; also contains graphic material (some col.). Includes abstract and vita. Advisor: Bradford T. Stokes, Dept. of Physiology and Cell Biology. Includes bibliographical references (p. 157-186).
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LeMoine, Dana. "Efficacy and Impacts of Perioperative Bupivacaine and Buprenorphine in a Rat Model of Thoracic Spinal Cord Injury." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu152421729752612.
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Heiden, Erin Ose. "Injuries among individuals with pre-existing spinal cord injury: understanding injury patterns, burdens, and prevention." Diss., University of Iowa, 2013. https://ir.uiowa.edu/etd/1624.
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As a growing body of research has focused on the individual, social, and environmental factors that facilitate life after spinal cord injury (SCI), particular emphasis has been placed on health conditions that are modifiable and preventable. Subsequent injuries are a serious health problem for individuals with SCI. They are a direct threat to further morbidity and mortality, and are both a cause and consequence other secondary health conditions.
As a first step toward understanding this public health problem, the purpose of this dissertation research was to describe the patterns, burdens, and prevention of subsequent injury among individuals with SCI. In three distinct, but related studies, this dissertation examined the characteristics of hospitalizations due to an injury among individuals with paraplegia, and compared the differences in length of stay (LOS) and hospital costs of injury hospitalizations between individuals with quadriplegia versus paraplegia. In addition, it explored the experience of subsequent injury among individuals with SCI who return to work and examined perceptions of threat and efficacy in preventing subsequent injury using the Extended Parallel Process Model. Using discharge level weighting available in the Nationwide Inpatient Sample, Study 1 calculated national estimates of injury hospitalizations for individuals with paraplegia by patient, hospital, and injury characteristics. Most injury hospitalizations occurred among males, to individuals 35-49 years, and were due to falls, poisonings, or motor vehicle traffic. With the same dataset, Study 2 used logistic regression to estimate the effect of patient characteristics on odds of hospitalized patients with quadriplegia versus paraplegia, and linear regression to estimate predicted differences in hospital costs for individuals with quadriplegia compared to paraplegia. Fewer injury hospitalizations but longer hospital stays, and higher hospital costs per discharge were found for individuals with quadriplegia compared to individuals with paraplegia. Males, younger age, and the uninsured were significant predictors of higher hospital costs. Finally, Study 3 used in-depth interviews to qualitatively explore the perceptions on subsequent injury among individuals with SCI who return to work, and found individuals with SCI who return to work recognized the importance of preventing subsequent injury, and were taking actions to prevent subsequent injury in their daily life and in the workplace.
The significance of this research is that it is the first description of injury hospitalizations for all causes of injury by specific type of SCI, and the associated medical outcomes of LOS and direct medical costs. Prevention of subsequent injury should be a priority. The perceptions of individuals with SCI about the severity of and their susceptibility to injury and the efficacy of individual and environmental actions to prevent subsequent injury described in this research should be used to inform the development of interventions that prevent subsequent injury.
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Aubé, Benoit. "Dynamics of myeloid cell infiltration and blood-spinal cord barrier disruption in a murine model of multiple sclerosis." Thesis, Université Laval, 2013. http://www.theses.ulaval.ca/2013/30428/30428.pdf.
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La rupture de la barrière hémoencéphalique (BHE) ainsi que l’infiltration cellulaire sont des évènements pathophysiologiques caractéristiques de la sclérose en plaques et de son modèle animal, l’encéphalomyélite autoimmune expérimentale (EAE). Cependant, leur relation avec l’évolution de l’EAE est obscure, notamment car les préparations histologiques standards recquièrent le sacrifice des animaux et nous privent d’informations cruciales quant à l’initiation, au développement et à la progression de la maladie. Nous utilisons le modèle EAE chez la lignée de souris lys-GFP ki, chez laquelle les cellules myéloïdes (i.e. neutrophiles et monocytes) expriment eGFP. De l’imagerie intravitale est effectuée à des moments précis, ce qui permet l’étude de l’infiltration cellulaire en plus de l’évaluation de l’intégrité de la barrière hémo-encéphalique (BHE) au cours de la pathologie. Les séances d’imagerie non-terminales offrent un contexte temporel considérable, puisqu’il est possible de suivre le développement de la maladie chez un animal qui a été précédemment imagé. La première étape a donc consisté à établir que la chirurgie et la séance d’imagerie n’avaient aucune influence sur le développement de l’EAE chez les animaux expérimentaux. Les résultats obtenus à l’aide d’imagerie intravitale tendent à démontrer qu’un affaiblissement de la BHE envers les molécules de petite taille (760 Da) est corrélé à l’infiltration de cellules GFP-positive dans la moelle épinière. Il est d’autant plus intéressant de constater que cette invasion cellulaire arrive en même temps que l’apparition des symptômes cliniques chez les animaux atteints d’EAE. Nous avançons l’hypothèse que les neutrophiles sont les cellules myéloïdes responsables de brèches initiales dans la BHE, qui influençent son intégrité aux stades précoces de la maladie. Des expériences de déplétion envers les neutrophiles ont donc été effectuées chez des animaux EAE afin de confirmer notre hypothèse. Les résultats suggèrent que les neutrophiles influencent l’initiation de la maladie et sa sévérité totale, en plus d’être intimement liés à l’état de la BHE tôt dans la pathologie.Blood-spinal cord barrier (BSCB) disruption and immune cell infiltration are early pathophysiological hallmarks of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Their relationship with the course of EAE remains unclear, however, notably because histological tissue preparations involve sacrifice and inherently result in the loss of crucial information regarding the initiation or development and progression of the disease. We use the EAE model in the lys-GFP ki mouse strain, in which blood-borne myeloid cells (i.e. neutrophils and monocytes) express eGFP. Intravital two-photon microscopy is performed at selected time points, enabling the investigation of cellular infiltration together with the assessment of the blood- barrier (BBB) integrity over the course of the pathology. Non-terminal imaging sessions offer extensive temporal context as it is possible to follow the development of the disease in an animal which has been previously imaged. One can appreciate the advantage of such a method as it is possible to relate, in the same animal, previous observations with clinical outcome. The first step thus consisted in establishing that the surgery and imaging session did not affect the development of EAE in experimental animals. Results obtained demonstrate that the permeability of the BBB to small molecular tracers (760 Da) correlates with the infiltration of GFP-positive myeloid cells into the spinal cord parenchyma. Interestingly, this cellular invasion is reminiscent of the appearance of clinical symptoms displayed by EAE animals. We put forward the hypothesis that neutrophils are the myeloid cells responsible for initial breaches in the BBB, influencing the latter’s integrity at early stages of the disease. Neutrophil depletion experiments have thus been performed in EAE mice in order to confirm this hypothesis. Results suggest that neutrophils influence the initiation and total severity of the disease, as well as being intimately linked to the status of the BBB early in the pathology.
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Olby, Natasha J. "An experimental model of rat spinal cord injury : its development and studies on manipulation of its glial environment." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243014.
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Fox, Jonathan Howard. "Spinal cord gene expression changes in the chicken (Gallus gallus) model of phenyl saligenin phosphate induced delayed neurotoxicity." Diss., Virginia Tech, 2002. http://hdl.handle.net/10919/27192.
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Some organophosphorus (OP) esters induce a central-peripheral distal axonopathy called organophosphorus ester-induced delayed neurotoxicity (OPIDN). In the chicken model neurological deficits and microscopic lesions develop 7-21 days after exposure. Neurotoxic esterase (NTE) is thought to be the initial target in OPIDN. Evidence indicates that neuropathic OP esters have to bind NTE and chemically ?age? for OPIDN induction. It was hypothesized that phenyl saligenin phosphate (PSP), a neuropathic OP ester that essentially irreversibly inhibits NTE as it undergoes the chemical aging process, results in changes in spinal cord gene expression that do not occur with phenylmethylsulfonyl fluoride (PMSF), a non-neuropathic compound that inhibits NTE without aging. This hypothesis was tested in Gallus gallus in experiments designed to detect differences in spinal cord gene expression between PSP, PMSF and vehicle-treated birds 24 hours after exposure. Two approaches were used. Targeted display was developed and used to screen approximately 15000 gel bands. Three candidate genes were identified by targeted display. One, designated P1 has 100% homology with expressed sequence tag pgp1n.pk010.m23, another, P2, is homologous to human KIAA1307, and a third, P3, is unidentified. Northern blotting was used to measure spinal cord expression of a-tubulin and other genes previously reported to be differentially expressed following exposure to di-isopropryl phosphorofluoridate, another agent causing OPIDN. Only expression of a-tubulin was altered in PSP-treated hens. Time course experiments were undertaken to determine spinal cord expression changes of P1, P2, P3 and a-tubulin transcripts at 12, 24, 36 and 48 hours post-exposure. Findings indicated decreases and increases, respectively, of P1 (22%, p=0.0011) and P2 (26%, p=0.0055) transcripts at 12 hours in PSP treated hen spinal cord compared to DMSO controls. An ~2.5 kb a-tubulin transcript was decreased across most time points with maximum change at 48 hours (33%, p=0.0479); an ~4.5 kb a-tubulin transcript was upregulated at 12 hours (38%, p=0.0125) and down regulated at 48 hours (28%, p=0.0576). Responses to PMSF were different than responses to PSP. Spinal cord in-situ hybridization experiments revealed, 1.) mainly neuronal expression of P1, P2 and a-tubulin transcripts, and, 2.) decreased expression of neuronal P1 and a-tubulin transcripts at 12 and 48 hours, respectively. Results indicate that PSP can induce changes in gene expression distinct from those induced with the non-neuropathic NTE inhibitor, PMSF. However, expression changes were low in frequency and magnitude, and their mechanistic importance remains to be fully established.Ph. D.
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Lopes, Maria José Cardoso. "Characterization of the glial scar tissue in a murine model of spinal cord compression, with focus on hyaluronan." Master's thesis, Universidade de Aveiro, 2015. http://hdl.handle.net/10773/15683.
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Mestrado em Biologia Molecular e CelularSpinal cord injury (SCI) is a devastating neurological disorder that affects thousands of people each year. Although in recent decades significant progress has been made in relation to understanding the molecular and cellular events underlying the nervous damage, spinal cord injury is still a highly disabling condition for which there is no curative therapy. People affected by spinal cord injuries manifested dysfunction or loss, temporary or permanent, of motor, sensory and / or autonomic functions depending on the spinal lesion damaged. Currently, the incidence rate of this type of injury is approximately 15-40 cases per million people worldwide. At the origin of these lesions are: road accidents, falls, interpersonal violence and the practice of sports. In this work we placed the hypothesis that HA is one of the component of the scar tissue formed after a compressive SCI, that it is likely synthetised by the perilesional glial cells and that it might support the permeation of the glial scar during the late phase of SCI. Nowadays, much focus is drawn on the recovery of CNS function, made impossible after SCI due to the high content of sulfated proteoglycans in the extracellular matrix. Counterbalancing the ratio between these proteoglycans and hyaluronic acid could be one of the experimental therapy to re-permeate the glial scar tissue formed after SCI, making possible axonal regrowth and functional recovery. Therefore, we established a model of spinal cord compression in mice and studied the glial scar tissue, particularly through the characterization of the expression of enzymes related to the metabolism of HA and the subsequent concentration thereof at different distances of the lesion epicenter. Our results show that the lesion induced in mice shows results similar to those produced in human lesions, in terms of histologic similarities and behavioral results. but these animals demonstrate an impressive spontaneous reorganization mechanism of the spinal cord tissue that occurs after injury and allows for partial recovery of the functions of the CNS. As regards the study of the glial scar, changes were recorded at the level of mRNA expression of enzymes metabolizing HA i.e., after injury there was a decreased expression of HA synthases 1-2 (HAS 1-2) and an increase of the expression HAS3 synthase mRNA, as well as the enzymes responsible for the HA catabolism, HYAL 1-2. But the amount of HA measured through the ELISA test was found unchanged after injury, it is not possible to explain this fact only with the change of expression of enzymes. At two weeks and in response to SCI, we found synthesized HA by reactive astrocytes and probably by others like microglial cells as it was advanced by the HA/GFAP+ and HA/IBA1+ cells co-location.
A lesão medular é uma desordem neurológica devastadora que afeta milhares de pessoas a cada ano. E apesar de nas últimas décadas ter sido feito um enorme progresso relativamente à compreensão dos eventos moleculares e celulares que este dano desencadeia, a lesão medular ainda é uma condição altamente incapacitante e mortal para a qual ainda não há cura. Os indivíduos que apresentam lesões medulares, manifestam disfunção ou perda, temporária ou permanente, das funções motoras, sensoriais e/ou autonómicas. Atualmente a taxa de incidência desta tipologia de lesões é de aproximadamente, 15-40 casos por milhão de pessoas em todo o mundo. Na origem destas lesões estão: acidentes rodoviários, quedas, violência interpessoal e a prática de desportos. Neste trabalho foi colocada a hipótese de que o ácido hialurónico (HA) seja um dos componentes do tecido cicatricial formado após a compressão medular e que provavelmente seja sintetizado pelas células gliais situadas à volta da lesão, podendo ajudar na penetração da cicatriz glial, por parte das células nervosas, durante uma fase mais tardia da lesão da espinal medula. Atualmente tem sido dada muita atenção ao restabelecimento da função do SNC, impossibilitado pelo elevado teor de proteoglicanos sulfatados na matriz extracelular. O contrabalanço do rácio entre o teor de proteoglicanos e de HA pode ser uma terapia experimental para a re-permeabilização do tecido da cicatriz glial formada após a lesão medular, possibilitando o crescimento axonal e a recuperação funcional. Por isso, estabeleceu-se um modelo de compressão da espinal medula em ratinhos e estudou-se o tecido da cicatriz glial, em particular, a caracterização da expressão de enzimas relacionadas com o metabolismo do HA e a sua posterior concentração a diferentes distâncias do epicentro da lesão. Os nossos resultados mostram que a lesão induzida em ratinhos produziu resultados semelhantes às lesões encontradas em humanos, tanto do ponto de vista histológico como funcional. No entanto, após traumatismo, estes animais demonstraram um mecanismo de recuperação espontânea impressionante na espinal medula resultando numa recuperação parcial da função do SNC. Quanto ao estudo da cicatriz glial, as alterações foram detetadas na expressão do mRNA das enzimas metabolizadoras de HA, isto é, após a lesão houve uma diminuição na expressão das HAS1-2 e um aumento na expressão de mRNA da sintase HAS3 assim como das enzimas ligadas à degradação do HA, HYAL 1-2. Porém, duas semanas após LM a concentração de HA medida através do teste ELISA encontrou-se inalterada. É impossível explicar este facto apenas com a mudança na expressão das enzimas ligadas ao HA. A duas semanas pós-trauma, em resposta à LM, encontrámos HA sintetizado por astrócitos reativos e, provavelmente, por outras células, como a microglia tal como foi avançado pela co-localização de HA/IBA1+ e HA/GFAP+.
Le traumatisme médullaire est une affection neurologique dévastatrice qui affecte des milliers de personnes chaque année. Bien que ces dernières décennies d'énormes progrès ont été fait par rapport à la compréhension des événements moléculaires et cellulaires qui déclenchent les dommages au sein du tissu nerveux, les dommages de la moelle épinière sont encore irréversibles et rendent les personnes atteintes très invalidées. Aucun traitement visant à remédier aux pertes fonctionnelles n’est disponible. Les gens atteints de traumatismes de la moelle épinière, manifestent un dysfonctionnement ou une perte, temporaire ou permanente, des fonctions motrice, sensorielle et / ou autonome. Actuellement, l’incidence de ce type de blessure est d'environ 15-40 cas par million de personnes dans le monde. L'origine de ces lésions sont: accidents de la route, chutes, violence interpersonnelle et pratique de sports. Dans ce travail, nous avons placé l'hypothèse que l'acide hyaluronique (HA) est l'un des composants du tissu cicatriciel formé après une compression de la moelle épinière, qu'il est probablement synthétisé par les cellules gliales péri lésionnelles et qu'il pourrait soutenir la pénétration de la cicatrice gliale pendant la phase tardive de la LM. Actuellement beaucoup d'attention est attirée sur le rétablissement de la fonction du système SNC, rendue impossible après la LM en raison de la contenu élevé en protéoglycanes sulfatés dans la matrice extracellulaire. Contrebalançant le rapport entre ces protéoglycanes et l'HA peut être une thérapie expérimentale de la re-pénétration dans le tissu de cicatrice gliale formé après la LM, ce qui rend possible le repousse axonale et la récupération fonctionnelle. Par conséquent, nous avons établi un modèle de compression de la moelle épinière chez des souris et étudié le tissu de la cicatrice gliale, en particulier par la caractérisation de l'expression des enzymes liées au métabolisme de l'HA et la concentration ultérieure de celui-ci à des distances différentes de l'épicentre de la lésion. Les résultats montrent que la lésion induite chez la souris produit des résultats similaires à ceux trouvés dans les lésions humaines, d'un point de vue fonctionnel et histologique. Toutefois, après un traumatisme, ces animaux ont démontré un mécanisme de récupération spontanée impressionnante dans la moelle épinière entraînant une reprise partielle de la fonction du système nerveux central. De manière surprenante, la quantité d'HA vérifiée par le test ELISA s’est trouvé inchangée deux semaines après traumatisme médullaire. Il est impossible d'expliquer ce fait uniquement avec le changement de l'expression d'enzymes liées à l'HA. Nous avons constaté que deux semaines après traumatisme, il ya l' HA synthétisé par les astrocytes réactifs et probablement par d'autres comme les cellules microgliales comme il a été avancé par les résultats de colocalisation de l' HA et cellules GFAP+ ainsi que l'HA et cellules IBA1+.
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Levine, Richard. "Evaluation of the Brainstem Spinal Cord Preparation in the Neonatal Rat as a Model for Prenatal Nicotine Exposure." The University of Arizona, 2012. http://hdl.handle.net/10150/623649.
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Class of 2012 AbstractSpecific Aims: The goal of this project was to evaluate the use of a preparation of the brainstem and spinal cord of neonatal rats that has been widely used for observing and quantifying central nervous activity, as well as the response to pharmacological manipulation. To achieve this, we specifically aimed to remove the intact brainstem and spinal cord of newborn rats, and develop a preparation that would maintain physiological function and allow for recording of electrical activity. Methods: Multiple dissections were performed on neonatal rats. Conditions during the dissections were controlled to maintain physiological function. Once removed, the intact brainstem and spinal cord was placed in a preparation that allowed for manipulation and access to nerve rootlets. Finally, glass suction electrodes were used to record electrical activity directly from the nerve rootlets. Once recorded, the data were stored on a hard drive for further analysis. Main Results: We were successful in isolating the intact brainstem and spinal cord in neonatal rats while maintaining physiological conditions and nervous activity. The preparation allowed for easy access to nerve roots as well as customization for different experiments. We were also successful in recording nerve activity in the preparation and collection of data for use in future experiments Conclusions: We conclude that the brainstem spinal cord preparation described in this study is a valuable tool that allows for recording and analysis of nerve activity, and specifically for measurement of respiratory motor output. This is a preparation that can be used in a variety of experiments that attempt to observe or quantify the activity of central nerve cells and allows for pharmacological interventions that could be applied in various experiments.
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Furmanski, Orion. "Manipulating Embryonic Neural Precursor Cells for Therapeutic Transplantation into a Rat Model of Neuropathic Pain." Scholarly Repository, 2009. http://scholarlyrepository.miami.edu/oa_dissertations/340.
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Persons with spinal cord injury (SCI) suffer life-long consequences including paralysis, loss of involuntary bodily functions, and chronic pain. A subset of SCI patients develop neuropathic pain (NP), a chronic condition resulting from damage to the spinal cord. Hyperexcitability of spinal cord sensory neurons near damaged tissue is believed to underlie SCI-related NP. Although many therapies have been employed clinically to combat SCI-NP, few give satisfactory long-term relief. Transplantation of cells that release GABA, a molecule that inhibits neuronal activity, is being explored as an alternative to current SCI-NP therapies. My experiments made progress toward preclinical modeling of GABA cell therapy for SCI-NP. First, I sought to determine whether quisqualic acid (QUIS)-induced SCI altered responses to tonic pain stimuli or altered GABAergic neural circuitry in rats. Second, I sought to determine whether a combination of genetic and trophic manipulations could promote a GABAergic phenotype in rat embryonic neural precursor cells (NPCs) in an in vitro culture system. The results revealed that QUIS-SCI rats exhibit unusually prolonged nocifensive responses to hind paw formalin injections. There was no significant difference between QUIS-SCI and sham surgery rats in c-Fos immunolabeling of spinal cord sensory neurons after formalin-induced neuronal activity. However, immunohistochemistry revealed substantial decreases in staining for markers of GABA presynaptic vesicles in injured spinal cord tissue. NPCs were enriched for a neuronal phenotype by combining withdrawal of the growth factor FGF-2 from culture media and overexpression of the transcription factor MASH1 in transfected cells. Although glial marker expression was suppressed in NPCs by these manipulations, expression of neuronal markers none the less declined through time. MASH1-overexpressing NPCs exhibited greater clonal expansion and decreased stress-induced PDI expression after FGF-2 withdrawal as compared to naïve. In light of existing data, these results suggest that the QUIS-SCI model may be useful for testing the efficacy of GABAergic NPC transplantation to reduce neuropathic pain. MASH1 overexpression and FGF-2 withdrawal could serve as a first step toward enriching GABA in NPCs for transplantation. Although the mechanism for MASH1 cytoprotection remains unclear, MASH1 may enhance survival of NPCs grafted into the spinal cord. These experiments contributed to the preclinical basis for application of therapeutic GABAergic stem cell transplantation for NP in human SCI patients.
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Narayan, Sreenath. "REANIMATION OF A DENERVATED MUSCLE USING UPPER MOTONEURON INJURED LOWER MOTONEURONS IN SPINAL CORD INJURY PATIENTS: A RAT MODEL." online version, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1133754830.
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Starkey, Michelle Louise. "Strategies to promote repair and restore function after spinal cord injury : the mouse as an in vivo model system." Thesis, King's College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.433905.
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Macaya, Daniel J. (Daniel Joseph). "Biomaterials-tissue interaction of an injectable collagen-genipin gel in a rodent hemi-resection model of spinal cord injury." Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/84410.
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Thesis (Ph. D. in Medical Engineering and Medical Physics)--Harvard-MIT Program in Health Sciences and Technology, 2013.Cataloged from PDF version of thesis.
Includes bibliographical references.
Spinal cord injury (SCI) is a significant health issue resulting in life-long disability and associated secondary complications, affecting approximately 300,000 individuals in the United States. Primary barriers to functional recovery after SCI include the formation of a growth inhibitory astrocyte scar at the lesion border and a lack of a supportive stroma within the defect allowing for axon regeneration. Interestingly, in animals capable of spinal cord regeneration, astrocytes create a tissue bridge across the injury site to facilitate the regeneration of axons through the defect and thus enable functional recovery. The overall goal of this thesis was to develop an injectable collagen-genipin (Col-Gen) hydrogel to facilitate the intrinsic regenerative response after SCI by promoting the population of the defect with astrocytes through a provisional scaffold pennissive of astrocyte migration. The specific aims of the thesis involved: 1) development and materials characterization of an injectable collagen hydrogel for neural tissue regeneration, capable of undergoing covalent crosslinking in vivo; 2) evaluation of the permissiveness of Col-Gen gels with and without Fibroblast growth factor-2 (FGF-2), a known astrocyte chemoattractant, incorporated within lipid microtubules (LMTs) to infiltration by primary astrocytes using an in vitro cellular outgrowth assay; 3) evaluation of select formulations of the gel, based on the in vitro findings, in a standardized hemi-resection defect in the rat spinal cord. Functional, locomotor, and histopathological outcome measures, recorded up to 4 weeks post-SCI were correlated with each other and with micro MRI studies. In vivo, the implantation of Col-Gen gels containing FGF-2 LMTs resulted in the enhancement of astrocyte, blood vessel, and laminin infiltration of the defect; increased the amount of spinal cord tissue spared from secondary degeneration; and increased functional recovery, at four weeks post injury as compared to control or Col-Gen treatment groups. Micro MRI was found to be a suitable modality to nondestructively observe the features of the injury in situ. This work commends an injectable, covalently cross-linkable formulation of collagen gel incorporating FGF-2-releasing LMTs for further investigation for the treatment of SCI.
by Daniel J. Macaya.
Ph.D.in Medical Engineering and Medical Physics
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McHenry, Colleen Louise. "A biomechanical model of femoral forces during functional electrical stimulation after spinal cord injury in supine and seated positions." Thesis, University of Iowa, 2010. https://ir.uiowa.edu/etd/710.
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Following a spinal cord injury (SCI), the paralyzed extremities undergo muscle atrophy and decrease in bone mineral density (BMD) due in part to the loss of physiological loading. It is crucial to prevent musculoskeletal deterioration so the population is less susceptible to fractures, and could take advantage of stem cell treatment if it becomes available. Functional electrical stimulation (FES) has been shown to advantageously train the paralyzed extremities. However, there is a risk of fracture during FES due to low BMD of individuals with SCI. Therefore, the forces generated during FES need to be modeled so researchers and clinicians safely administer this intervention.
The purpose of this project was to develop a biomechanical or mathematical model to estimate the internal compressive and shear forces at the distal femur, a common fracture site for individuals with SCI during FES. Therefore, a two-dimensional static model was created of the lower extremity in the supine and seated positions. The compressive and shear forces at the distal femur were estimated for both positions during FES. These internal compressive and shear forces estimated at the distal femur by the supine model were compared to those estimated by the standing model. Also, for the seated model, the compressive and shear forces at the distal femur estimated by a tetanic muscle contraction were compared to those estimated by a doublet muscle contraction. Finally, the supine model was validated using experimental testing.
The primary findings are 1) the standing model estimated more compressive force and less shear force at the distal femur compared to the supine model when position and quadriceps muscle force remain constant and 2) for the seated model, a tetanic quadriceps muscle contraction predicts greater compressive and shear at the distal femur compared to a doublet muscle contraction. Also the validation testing revealed a 3.4% error between the supine model and the experimental testing. These models provide valuable insights into the internal forces at the distal femur during FES for those with SCI.
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Scesa, G. "MOLECULAR ASPECTS OF THERAPEUTIC ACTION OF 3° TRIMESTER AMNIOTIC FLUID CELLS IN A MOUSE MODEL OF SPINAL CORD INJURY." Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/245779.
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Spinal cord injury (SCI) is a disabling degenerative disease that heavily impacts on patient's life. To date, treatments available are mostly vain, thought to target the inflammatory processes sustaining the secondary damage: in this scenario, the use of stem cells represents a promising new therapeutic strategy as it might permit a complete recovery of the patient through a regeneration of damaged nerve fibers. Among the different type of stem cells available, we focused on 3° trimester amniotic fluid-derived cells (Afs), verifying their potential therapeutic activity on a mouse model of SCI.
Only the cultures expressing NG2 were able to elicit an improvement in the motor performance, obtained through a better preservation of damaged tissue. It was observed a higher angiogenesis in the perilesion area, sustained by an upregulation of the pro-angiogenic genes HIF-1α and VEGF; furthermore macrophage infiltration levels were significantly reduced in cells treated mice compared to controls. The Hepatocyte Growth Factor (HGF) mRNA and protein levels resulted higher in the filtering organs, as the lungs, and in the bloodstream of transplanted animals, suggesting an endocrine effect of the cells.
The ability of the cells to produce HGF was confirmed in vitro, after stimulation with proinflammatory cytokines, like IL1-β and LPS, suggesting the cells might be responsive to an environment-induced activation.
Given these results, AFs demonstrated to exert a therapeutic effect in our animal model of spinal cord injury.
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Sheehy, Susan Budassi. "A nurse-coached exercise intervention to increase muscle strength, improve quality of life, and increase self-efficacy in people with tetraplegic spinal cord injuries: A single subject design study." Thesis, Boston College, 2010. http://hdl.handle.net/2345/1411.
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Thesis advisor: Mary E. DuffyTen people with tetraplegic spinal cord injuries participated in a nurse-coached exercise intervention/single subject design study over a period of six months. Four pieces of exercise equipment were used: the RT300S Functional Electrical Stimulation Bike, the VIta Glide, the NuStep TRS 4000, and the Easy Stand Evolv Glider. Measurement of variables of the Manual Muscle Test (MMT), Catz-Itzkovich Spinal Cord Independence Measures (CI-SCIM), and Moorong Self-Efficacy Scale (MSES) were collected at baseline, at three months into the exercise intervention, and at six months (at the conclusion of the intervention). Results were determined by visual analysis of graphs, in keeping with single subject design methods, and statistical analysis of combined data. Of those muscles that demonstrated some strength at baseline, 75% experienced increased strength at three and/or six months into the intervention. Of those muscles that demonstrated no strength at baseline and that were adjacent to muscles that demonstrated some strength at baseline, 66% were found to have increased strength at three and/or six months. Nine of ten participants experienced upward trends in CI-SCIM scores overall (p<.0001). The results of the subscales of Self-Care (p<.0001) and Mobility (p<.0001) indicated statistically significant changes over time. The subscale Respiratory and Sphincter Management was not statistically significant (p>.05). Visual analysis of graphs demonstrated that each of ten participants experienced strong improvements in self-efficacy scores from baseline to three months and from three months to six months into the intervention. R-ANOVA (p<.0001) confirmed statistical significance across ten participants. The Sheehy Spinal Cord Injury Functional Improvement Via Exercise (SCI-FIVE) Model was constructed prior to the study and validated throughout the course of the study. The results of the study validated all components of the Model and demonstrated increased muscle strength, increased self-efficacy, and improved quality of life for the ten study participants who participated in a nurse-coached exercise intervention for people with tetraplegic spinal cord injuries
Thesis (PhD) — Boston College, 2010
Submitted to: Boston College. Connell School of Nursing
Discipline: Nursing
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Russell, Colin Macdonald. "A nonlinear finite element model of the rat cervical spine : validation and correlation with histological measures of spinal cord injury." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/43119.
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Researchers and clinicians do not currently use the heterogeneity of the primary mechanism of spinal cord injury (SCI) to tailor treatment strategies because the effects of these distinct patterns of acute mechanical damage on long-term neuropathology have not been fully investigated. Computational modelling of SCI enables the analysis of mechanical forces and deformations within the spinal cord tissue that are not visible experimentally. I created a dynamic, hyperviscoelastic three-dimensional finite element (FE) model of the rat cervical spine and simulated contusion and dislocation SCI mechanisms. I investigated the relationship between maximum principal strain and previously published tissue damage patterns, and compared primary injury patterns between mechanisms.
My model incorporates the spinal cord white and gray matter, dura mater, cerebrospinal fluid, spinal ligaments, intervertebral discs, a rigid indenter and vertebrae, and failure criteria for ligaments and vertebral endplates. High-speed (1 m/s) contusion and dislocation injuries were simulated between vertebral levels C3 and C6 to match previous animal experiments, and average peak maximum principal strains were calculated for several regions at the injury epicentre and at 1 mm intervals from +5 mm rostral to -5 mm caudal to the lesion. I compared average peak principal strains to tissue damage measured previously via axonal permeability to 10 kD fluorescein-dextran (Choo, 2007). Linear regression of tissue damage against peak maximum principal strain for pooled data within white matter regions yields significant (p < 0.0001) correlations that are similar for both contusion (R² = 0.86) and dislocation (R² = 0.54).
With additional simulations of cord contusion injuries at lower injury velocities of 3 and 300 mm/s, I found that current material properties used to model the cord are not biofidelic within this velocity range. By fitting existing experimental cord material testing data and plotting alongside the material properties used in several related models, I further demonstrated the remaining divide between experimental data and computational models.
My model enhances our understanding of the differences in injury patterns between SCI mechanisms, and provides further evidence for the link between principal strain and tissue damage. Furthermore, my results speak to a continued need to test cord material properties at a range of strains and strain rates to better refine cord hyperviscoelastic properties.
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Tüngler, Victoria [Verfasser]. "Progesterone's activity in the central nervous system : a murine model study on Gliotoxin injured Myelin of the spinal cord / Victoria Tüngler." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2011. http://d-nb.info/1029846049/34.
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Shah, Adhvait M. "An injectable gelatin-based conjugate incorporating EGF promotes tissue repair and functional recovery after spinal cord injury in a rat model." Thesis, Massachusetts Institute of Technology, 2019. https://hdl.handle.net/1721.1/122195.
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This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Thesis: Ph. D. in Medical Engineering and Medical Physics, Harvard-MIT Program in Health Sciences and Technology, 2019
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references.
Spinal cord injury (SCI) is a devastating condition drastically reducing the quality of life that affects about 300,000 patients in the USA. As a result of the injury, sensory perception and motor functions are lost. Current treatments do not address the root cause - degeneration and loss of neural tissue. The overall goal of this pre-clinical work was to evaluate a novel gelatin-based conjugate (gelatin-hydroxyphenyl propionic acid; Gtn-HPA) capable of undergoing covalent cross-linking in vivo after being injected as a liquid. Gtn-HPA incorporating epidermal growth factor (EGF) and/or stromal cell-derived factor - 1ɑ (SDF-1ɑ) was evaluated for promoting tissue healing and functional recovery using a standardized 2-mm hemi-resection SCI rat model, four weeks after injection. Injection of Gtn-HPA/EGF immediately after the surgical excision injury significantly improved motor functional recovery, compared to gel alone and non-treated controls.
Bladder function was also improved in Gtn-HPA/EGF-treated animals. Functional improvement correlated with the amount of spared tissue. The volume of gel in the defects was quantified by a newly developed MRI-based method employing T1-weighted inversion recovery to unambiguously image Gtn-HPA in the injury site in a non-destructive manner. Histological analysis showed the presence of multiple islands of Gtn-HPA in the injury site after four weeks. There was a significantly greater number of cells migrating into the Gtn-HPA/EGF, compared to the gel alone, and these cells displayed neural progenitor cell markers: nestin, vimentin, and Musashi. The cells infiltrating Gtn- HPA were negative for glial fibrillary acidic protein (GFAP), a marker for astrocytes. Injection of the gel reduced the reactive astrocytic presence at the border outlining the injury site indicating the reduction of glial scar.
There was no notable inflammatory response to the Gtn-HPA gel, reflected in the number of CD68-positive cells, including macrophages. Of note was the demonstration by immunohistochemistry that the Gtn-HPA remaining at 4 weeks post-injection contained EGF. MMP2 was found to be playing a role in in vivo degradation of the Gtn-HPA gel. Additional behavioral and histological results were acquired injecting Gtn-HPA/EGF in 2-mm complete resection SCI rat model. Collectively, the findings signaled that injury sites injected with Gtn-HPA/EGF had greater potential for regeneration. In summary, this work commends an injectable, covalently cross-linkable formulation of Gtn-HPA incorporating EGF for further investigation in promoting functional recovery and potential regeneration for treatment of SCI and thereby improve the quality of life of SCI patients.
by Adhvait M. Shah.
Ph. D. in Medical Engineering and Medical Physics
Ph.D.inMedicalEngineeringandMedicalPhysics Harvard-MIT Program in Health Sciences and Technology
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Moulson, Aaron Jack Taylor. "Characterization of oligodendrocyte lineage cell responses remote to the lesion site in a murine model of thoracic contusion spinal cord injury (SCI)." Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/60315.
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Traumatic injury to the adult mammalian central nervous system (CNS) commonly results in permanent functional impairment due to the inability of injured CNS neurons to mount an effective regenerative response. Injury to the spinal cord is associated with a range of sensory, motor, and autonomic deficits, the most severe of which is complete paralysis. At a histological level, injury induced pathophysiological processes have been thoroughly characterized for the tissue area immediately surrounding the lesion epicentre, however remote to the lesion these changes are less well described. Previous studies have demonstrated that various perturbations, including traumatic injury, demyelination, artificial neural stimulation, neurodegeneration, and social experience, among others, induce robust oligodendrocyte precursor cells (OPC) responses, which function as endogenous precursors for myelinating oligodendrocytes. De novo myelination in the adult CNS has been implicated in motor learning, memory, and optimization of neural network function, thought to represent a potent form of neural plasticity. The demonstration of robust OPC proliferation and oligodendrogenesis in models of dorsal rhizotomy, axotomy, and axon degeneration, combined with the robust OPC responses characteristic of SCI lesion epicentres, lead us to hypothesize that contusion SCI would induce significant responses in resident OPC populations remote to the lesion site (specifically comprised of OPC proliferation, oligodendrogenesis, and new myelination). This may be functionally relevant to myelin plasticity on spared motor and sensory tracts remote to the lesion. To test this hypothesis, we conducted an in vivo study employing transgenic mouse lines (i.e. PDGFRα-CreERT:ROSA26-YFP and PDGFRα-CreERT:ROSA26-mGFP) that enabled the visualization and fate-mapping of OPCs and their progeny in the adult murine spinal cord following a moderate (70 Kdyne) T9-T10 thoracic contusion injury. Consistent with our predictions, we observed robust OPC proliferation and oligodendrogenesis remote to the lesion in both the cervical and lumbar spinal cord. Surprisingly, this did not manifest as increased new myelination, attributed (at least in part) to an observed maturation impairment of newly-formed oligodendrocytes.Science, Faculty of
Zoology, Department of
Graduate
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Cheng, Tianci [Verfasser], and Matthias [Akademischer Betreuer] Morgalla. "GABAergic neural stem cells transplantation after spinal cord injury induced chronic neuropathic pain in a rat model / Tianci Cheng ; Betreuer: Matthias Morgalla." Tübingen : Universitätsbibliothek Tübingen, 2019. http://d-nb.info/1182985920/34.
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Painter, Palak Rajeshkumar. "Quantitative analysis of glycinergic neurons including Ia inhibitory interneurons in the ventral spinal cord using a BAC-GlyT2-eGFP transgenic mouse model." Wright State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=wright1347911464.
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