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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Blood Supply and Vascular Reactivity of the Spinal Cord Under Normal and Pathological Conditions

January 2016 (has links)
abstract: The unique anatomical and functional properties of vasculature determine the susceptibility of the spinal cord to ischemia. The spinal cord vascular architecture is designed to withstand major ischemic events by compensating blood supply via important anastomotic channels. One of the important compensatory channels of the arterial basket of the conus medullaris (ABCM). ABCM consists of one or two arteries arising from the anterior spinal artery (ASA) and circumferentially connecting the ASA and the posterior spinal arteries. In addition to compensatory function, the arterial basket can be involved in arteriovenous fistulae and malformations of the conus. The morphometric anatomical analysis of the ABCM was performed with emphasis on vessel diameters and branching patterns. A significant ischemic event that overcomes vascular compensatory capacity causes spinal cord injury (SCI). For example, SCI complicating thoracoabdominal aortic aneurysm repair is associated with ischemic injury. The rate of this devastating complication has been decreased significantly by instituting physiological methods of protection. Traumatic spinal cord injury causes complex changes in spinal cord blood flow (SCBF), which are closely related to a severity of injury. Manipulating physiological parameters such as mean arterial pressure (MAP) and intrathecal pressure (ITP) may be beneficial for patients with a spinal cord injury. It was discovered in a pig model of SCI that the combination of MAP elevation and cerebrospinal fluid drainage (CSFD) significantly and sustainably improved SCBF and spinal cord perfusion pressure. In animal models of SCI, regeneration is usually evaluated histologically, requiring animal sacrifice. Thus, there is a need for a technique to detect changes in SCI noninvasively over time. The study was performed comparing manganese-enhanced magnetic resonance imaging (MEMRI) in hemisection and transection SCI rat models with diffusion tensor imaging (DTI) and histology. MEMERI ratio differed among transection and hemisection groups, correlating to a severity of SCI measured by fraction anisotropy and myelin load. MEMRI is a useful noninvasive tool to assess a degree of neuronal damage after SCI. / Dissertation/Thesis / Doctoral Dissertation Neuroscience 2016
2

Neuroprotective Drug Delivery to the Injured Spinal Cord with Hyaluronan and Methylcellulose

Kang, Catherine 13 August 2010 (has links)
Traumatic spinal cord injury (SCI) is a devastating condition for which there is no effective clinical treatment. Neuroprotective molecules that minimize tissue loss have shown promising results; however systemic delivery may limit in vivo benefits due to short systemic half-life and minimal passage across the blood-spinal cord barrier. To overcome these limitations, an injectable intrathecal delivery vehicle comprised of hyaluronan and methylcellulose (HAMC) was developed, and previously demonstrated to be safe and biocompatible intrathecally. Here, HAMC was determined to persist in the intrathecal space for between 4-7 d in vivo, indicating it as an optimal delivery system for neuroprotective agents to reduce tissue degeneration after SCI. HAMC was then investigated as an in vivo delivery system for two neuroprotective proteins: erythropoietin (EPO) and fibroblast growth factor 2 (FGF2). Both proteins demonstrated a diffusive release profile in vitro and maintained significant bioactivity during release. When EPO was delivered intrathecally with HAMC to the injured spinal cord, reduced cavitation in the tissue and significantly improved neuron counts were observed relative to the conventional delivery strategies of intraperitoneal and intrathecal bolus. When FGF2 was delivered intrathecally from HAMC, therapeutic concentrations penetrated into the injured spinal cord tissue for up to 6 h. Poly(ethylene glycol) modification of FGF2 significantly increased the amount of protein that diffused into the tissue when delivered similarly. Because FGF2 is a known angiogenic agent, dynamic computed tomography was developed for small animal serial assessment of spinal cord hemodynamics. Following SCI and treatment with FGF2 from HAMC, moderate improvement of spinal cord blood flow and a reduction in permeability were observed up to 7 d post-injury, suggesting that early delivery of neuroprotective agents can have lasting effects on tissue recovery. Importantly, the entirety of this work demonstrates that HAMC is an effective short-term delivery system for neuroprotective agents by improving tissue outcomes following traumatic SCI.
3

Neuroprotective Drug Delivery to the Injured Spinal Cord with Hyaluronan and Methylcellulose

Kang, Catherine 13 August 2010 (has links)
Traumatic spinal cord injury (SCI) is a devastating condition for which there is no effective clinical treatment. Neuroprotective molecules that minimize tissue loss have shown promising results; however systemic delivery may limit in vivo benefits due to short systemic half-life and minimal passage across the blood-spinal cord barrier. To overcome these limitations, an injectable intrathecal delivery vehicle comprised of hyaluronan and methylcellulose (HAMC) was developed, and previously demonstrated to be safe and biocompatible intrathecally. Here, HAMC was determined to persist in the intrathecal space for between 4-7 d in vivo, indicating it as an optimal delivery system for neuroprotective agents to reduce tissue degeneration after SCI. HAMC was then investigated as an in vivo delivery system for two neuroprotective proteins: erythropoietin (EPO) and fibroblast growth factor 2 (FGF2). Both proteins demonstrated a diffusive release profile in vitro and maintained significant bioactivity during release. When EPO was delivered intrathecally with HAMC to the injured spinal cord, reduced cavitation in the tissue and significantly improved neuron counts were observed relative to the conventional delivery strategies of intraperitoneal and intrathecal bolus. When FGF2 was delivered intrathecally from HAMC, therapeutic concentrations penetrated into the injured spinal cord tissue for up to 6 h. Poly(ethylene glycol) modification of FGF2 significantly increased the amount of protein that diffused into the tissue when delivered similarly. Because FGF2 is a known angiogenic agent, dynamic computed tomography was developed for small animal serial assessment of spinal cord hemodynamics. Following SCI and treatment with FGF2 from HAMC, moderate improvement of spinal cord blood flow and a reduction in permeability were observed up to 7 d post-injury, suggesting that early delivery of neuroprotective agents can have lasting effects on tissue recovery. Importantly, the entirety of this work demonstrates that HAMC is an effective short-term delivery system for neuroprotective agents by improving tissue outcomes following traumatic SCI.
4

Etude de la perfusion médullaire après lésion traumatique de la moelle épinière à dure-mère intacte / Study of spinal cord blood flow after spinal cord injury with intact dura mater

Soubeyrand, Marc 10 October 2012 (has links)
Après un traumatisme de la moelle épinière (TM), l’ischémieest un facteur d’aggravation des lésions. Cette ischémie peut être aggravée par l’augmentation depression du liquide cérébro-spinal (LCS) par le biais d’un effet tamponnade. Or chez l’homme,après un TM avec préservation de l’intégrité de la dure-mère, la pression de LCS augmentesignificativement. On suppose donc que le maintien d’une pression de LCS à des valeursphysiologique pourrait être une méthode de limitation de l’ischémie post-traumatique et doncd’amélioration du pronostic fonctionnel. Afin de pouvoir réaliser une étude expérimentale de cesphénomènes, nous avons consacré la première partie expérimentale de cette thèse à la mise au pointd’un modèle de TM à dure-mère intacte chez le rat permettant la mesure simultanée de la pressionde LCS et de la perfusion médullaire. Nous avons confirmé expérimentalement que la pression deLCS augmente après TM. Dans la seconde partie expérimentale, nous avons mis au point unetechnique expérimentale de quantification spatiale et temporelle de la perfusion médullaire grâce àl’échographie de contraste. Cette technique permettait aussi un suivi en temps réel de l’évolution dusaignement intra-parenchymateux induit par le TM. Dans la troisième partie expérimentale, nousavons utilisé notre modèle couplé avec l’échographie de contraste et le laser Doppler pour évaluerles effets de la noradrénaline injectée à la phase aigüe d’un TM sur la perfusion médullaire et lesaignement intra-parenchymateux. Nous avons montré que la noradrénaline augmentait trèslégèrement le flux sanguin superficiel mais pas le flux sanguin profond et qu’elle augmentait lataille du saignement. / After spinal cord injury (SCI), ischaemia aggravates lesions.Increase in cerebrospinal fluid (CSF) pressure can worsens ischaemia through a tamponnade effect.In humans, it has been shown that after SCI with intact dura mater, CSF pressure significantlyincreases. Therefore, preserving CSF pressure within a physiological range may limit post-traumaischaemia and improve neurological outcome. In order to experimentally study these phenomenon,we have dedicated the first part of that work to create a model of SCI in rats preserving dura’sintegrity and allowing simultaneous measurement of spinal cord blood flow (SCBF) and CSFpressure. We have confirmed that CSF pressure increases after SCI with intact dura. In the secondexperimental part, we have developed a technique allowing to perform spatial and temporalmeasurement of SCBF thanks to contrast enhanced ultrasonography (CEU). Moreover, thistechnique allows real-time measurement of the size of the parenchymal hemorrhage. In the thirdexperimental part, we have used our experimental model in association with CEU and LaserDoppler to assess the effects of early injection of norepinephrine on SCBF and parenchymalhemorrhage. We found that norepinephrine induces a slight increase in superficial SCBF while itdoesn’t modify deep SCBF and significantly increases the size of parenchymal hemorrhage.
5

Caractérisation du couplage neurovasculaire de la moelle épinière du rat

Paquette, Thierry 04 1900 (has links)
Dans le système nerveux central, l'activation d'un groupe de neurones entraine une augmentation locale du débit sanguin pour répondre à leurs besoins métaboliques accrus. Cette relation, connue sous le nom de couplage neurovasculaire (CNV), est essentielle pour utiliser l'imagerie par résonance magnétique fonctionnelle (IRMf) en recherche et en clinique. En effet, grâce au CNV, il est possible d'inférer l'activité neuronale à partir des réponses hémodynamiques mesurées lors des scans d’IRMf. Comprendre précisément le CNV est essentiel pour évaluer de manière fiable les changements fonctionnels dans la moelle épinière, notamment lors de pathologies ou de traitements qui affectent cette région. De plus, une connaissance approfondie du CNV permet de développer de nouvelles stratégies thérapeutiques ciblant les dysfonctionnements neurovasculaires. Bien que le CNV du cortex cérébral soit bien documenté, les informations concernant le CNV de la moelle épinière restent insuffisantes, comme souligné dans notre revue de littérature (chapitre 2). Ce manque de données sur le CNV de la moelle épinière peut entrainer des suppositions incorrectes si les propriétés du CNV cérébral sont appliquées de manière inappropriée à la moelle épinière. Ainsi, dans cette thèse, nous explorons la régulation du CNV de la moelle épinière en réponse à diverses conditions associées à la douleur, qui influencent généralement le CNV cérébral. Les conditions étudiées incluent l'effet de l’anesthésie à l'isoflurane (chapitre 3), les variations de la pression artérielle systémique (chapitre 4), la dysrégulation des astrocytes (chapitre 5), et les impacts de la douleur lombaire chronique (chapitre 6). Les méthodes comprenaient l'utilisation simultanée d’une multiélectrode et d'une sonde laser Doppler pour mesurer respectivement l'activité neuronale et le débit sanguin local dans la corne dorsale de la moelle épinière chez des rats Wistar, lors de stimulations électriques graduées du nerf sciatique. Nos résultats indiquent que le CNV reste stable malgré l'exposition à l'isoflurane à 1.2%, soutenant l'utilisation de cet anesthésiant général dans les études subséquentes de cette thèse. 6 Nos expérimentations ont révélé que les réponses hémodynamiques locales de la moelle épinière ne sont pas confondues par des changements significatifs de la pression artérielle induits par des stimulations nociceptives, assurant ainsi la constance du CNV. Par ailleurs, dans notre modèle de douleur chronique lombaire, induit par l'injection de l'adjuvant de Freund, connu pour entrainer de la neuroinflammation, nous avons observé que le CNV de la moelle épinière restait stable. Cette stabilité du CNV a été maintenue malgré l'émergence d'une hypersensibilité mécanique primaire et secondaire, révélant une sensibilisation centrale. Cependant, l'inhibition pharmacologique des astrocytes a altéré le CNV en réduisant les réponses hémodynamiques aux stimulations électriques, ce qui met en évidence le rôle crucial des astrocytes dans la modulation du CNV. Toutefois, nous avons observé que le décours temporel des réponses hémodynamiques locales est modifié par l'isoflurane et par les processus reliés à la douleur chronique. Par conséquent, même si la précision des interprétations des résultats de l'IRMf spinale est généralement validée par nos études, les changements de latence que nous avons observés exigent une analyse minutieuse des signaux d'IRMf spinale dans ces contextes spécifiques. De plus, compte tenu de l'impact significatif de la dysrégulation des astrocytes sur le CNV, nous recommandons d’interpréter avec prudence les résultats d'IRMf spinale dans des conditions similaires. En conclusion, cette thèse approfondit notre compréhension du CNV dans la moelle épinière, mettant en lumière l’unicité du CNV spinal par rapport à celui du cerveau. / In the central nervous system, the activation of a group of neurons leads to a local increase in blood flow to meet their increased metabolic needs. This relationship, known as neurovascular coupling (NVC), is crucial for the use of functional magnetic resonance imaging (fMRI) in research and clinical settings. Indeed, NVC allows for the inference of neuronal activity from measurements of hemodynamic responses. Precisely understanding NVC is essential for reliably assessing functional changes in the spinal cord, particularly in pathologies or treatments affecting this region. Moreover, a deep knowledge of NVC enables the development of new therapeutic strategies targeting neurovascular dysfunctions. Although NVC of the cerebral cortex is well-documented, information regarding spinal cord NVC remains insufficient, as highlighted in our literature review (Chapter 2). This lack of data on spinal NVC may lead to incorrect assumptions if cerebral NVC properties are inappropriately applied to the spinal cord. Thus, in this thesis, we explore the regulation of spinal NVC in response to various conditions associated with pain, which generally influence cerebral NVC. The conditions studied include the effect of isoflurane anesthesia (Chapter 3), variations in systemic blood pressure (Chapter 4), dysregulation of astrocytes (Chapter 5), and the impacts of chronic lumbar pain (Chapter 6). The methods included the simultaneous use of multi-electrodes and a laser Doppler probe to measure neuronal activity and local blood flow in the dorsal horn of the spinal cord in Wistar rats during graded electrical stimulations of the sciatic nerve. Our results indicate that NVC remains stable despite exposure to 1.2% isoflurane, supporting the use of this anesthetic in subsequent studies of this thesis. Our experiments revealed that local hemodynamic responses in the spinal cord are not confounded by significant changes in blood pressure induced by nociceptive stimulations, thus ensuring the consistency of NVC. Additionally, in a model of chronic lumbar pain induced by Freund's adjuvant injection, which is known to cause neuroinflammation, NVC remained stable despite the emergence of primary and secondary hypersensitivity, a sign of central sensitization. However, the 8 pharmacological inhibition of astrocytes altered NVC by reducing hemodynamic responses to electrical stimulations, highlighting the crucial role of astrocytes in modulating NVC. However, we demonstrate that the temporal course of local hemodynamic responses is altered by isoflurane and the processes associated with chronic pain. Therefore, although the accuracy of the interpretations of spinal fMRI results is generally validated by our studies, the latency changes of vascular responses in the aforementioned conditions, as well as the impact of astrocyte dysregulation, urge us to interpret these results with caution. In summary, this thesis enhances our understanding of NVC in the spinal cord, while illustrating significant differences with cerebral NVC, except in the essential role of astrocytes.

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