Dissertations / Theses on the topic 'Cerebrospinal fluid'
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Smuts, Heidi Esther Marie. "Isotachophoresis of human cerebrospinal fluid." Thesis, University of Cape Town, 1986. http://hdl.handle.net/11427/26160.
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Nikkilä, Heikki. "Cerebrospinal fluid cytology in schizophrenia." Helsinki : University of Helsinki, 2000. http://ethesis.helsinki.fi/julkaisut/laa/kliin/vk/nikkila/.
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Cardillo, Giulia. "Fluid Dynamic Modeling of Biological Fluids : From the Cerebrospinal Fluid to Blood Thrombosis." Thesis, Institut polytechnique de Paris, 2020. http://www.theses.fr/2020IPPAX110.
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Dans cette thèse, trois modèles mathématiques ont été proposés, avec l’objectif de modéliser autant d’aspects complexes de la biomédecine, dans lesquels la dynamique des fluides du système joue un rôle fondamental: i) les interactions fluide-structure entre la pulsatilité du liquide céphalo-rachidien et la moelle épinière (modélisation analytique); ii) dispersion efficace d’un médicament dans l’espace sous-arachnoïdien (modélisation numérique); et iii) la formation et l’évolution d’un thrombus au sein du système cardiovasculaire (modélisation numérique).Le liquide céphalorachidien est un fluide aqueux qui entoure le cerveau et la moelle épinière afin de les protéger. Une connaissance détaillée de la circulation du liquide céphalorachidien et de son interaction avec les tissus peut être importante dans l’étude de la pathogenèse de maladies neurologiques graves, telles que la syringomyélie, un trouble qui implique la formation de cavités remplies de liquide (seringues) dans la moelle épinière.Par ailleurs, dans certains cas, des analgésiques - ainsi que des médicaments pour le traitement de maladies graves telles que les tumeurs et les infections du liquide céphalorachidien - doivent être administrés directement dans le liquide céphalorachidien. L’importance de connaître et de décrire l’écoulement du liquide céphalorachidien, ses interactions avec les tissus environnants et les phénomènes de transport qui y sont liés devient claire. Dans ce contexte, nous avons proposé: un modèle capable de décrire les interactions du liquide céphalo-rachidien avec la moelle épinière, considérant cela, pour la première fois, comme un milieu poreux imprégné de différents fluides (sang capillaire et veineux et liquide céphalo-rachidien); et un modèle capable d’évaluer le transport d’un médicament dans l’espace sousarachnoïdien, une cavité annulaire remplie de liquide céphalo-rachidien qui entoure la moelle épinière.Avec le troisième modèle proposé, nous entrons dans le système cardiovasculaire.Dans le monde entière, les maladies cardiovasculaires sont la cause principale de mortalité. Parmi ceux-ci, nous trouvons la thrombose, une condition qui implique la formation d’un caillot à l’intérieur d’un vaisseau sanguin, qui peut causer sa occlusion. À cet égard, un modèle numérique a été développé qui étudie la formation et l’évolution des thrombus, en considérant simultanément les aspects chimico-biomécaniques et dynamiques des fluides du problème. Dans le modèle proposé pour la première fois, l'importance du rôle joué par les gradients de contrainte de cisaillement dans le processus de thrombogenèse est pris en compte.Les modèles sélectionnés ont fourni des résultats intéressants. Tout d’abord, l’étude des interactions fluide-structure entre le liquide céphalo-rachidien et la moelle épinière a mis en évidence es conditions pouvant induire l’apparition de la syringomyélie. Il a été observé comment la déviation des valeurs physiologiques du module d’Young de la moelle épinière, les pressions capillaires dans l’interface moelle-espace sousarachnoïdien et la perméabilité des compartiments capillaire et veineux, conduisent à la formation de seringues.Le modèle de calcul pour l’évaluation de la dispersion pharmacologique dans l’espace sousarachnoïdien a permis une estimation quantitatif de la diffusivité effective du médicament, une quantité qui peut aider à l’optimisation des protocoles d’injections intrathécales.Le modèle de thrombogenèse a fourni un instrument capable d’étudier quantitativement l’évolution des dépôts de plaquettes dans la circulation sanguine. En particulier, les résultats ont fourni des informations importantes sur la nécessité de considérer le rôle de l’activation mécanique et de l’agrégation des plaquettes aux côtés de la substance chimiqueIn the present thesis, three mathematical models are described. Three different biomedical issues, where fluid dynamical aspects are of paramount importance, are modeled: i) Fluid-structure interactions between cerebro-spinal fluid pulsatility and the spinal cord (analytical modeling); ii) Enhanced dispersion of a drug in the subarachnoid space (numerical modeling); and iii) Thrombus formation and evolution in the cardiovascular system (numerical modeling).The cerebrospinal fluid (CSF) is a liquid that surrounds and protects the brain and the spinal cord. Insights into the functioning of cerebrospinal fluid are expected to reveal the pathogenesis of severe neurological diseases, such as syringomyelia that involves the formation of fluid-filled cavities (syrinxes) in the spinal cord.Furthermore, in some cases, analgesic drugs -- as well drugs for treatments of serious diseases such as cancers and cerebrospinal fluid infections -- need to be delivered directly into the cerebrospinal fluid. This underscores the importance of knowing and describing cerebrospinal fluid flow, its interactions with the surrounding tissues and the transport phenomena related to it. In this framework, we have proposed: a model that describes the interactions of the cerebrospinal fluid with the spinal cord that is considered, for the first time, as a porous medium permeated by different fluids (capillary and venous blood and cerebrospinal fluid); and a model that evaluates drug transport within the cerebrospinal fluid-filled space around the spinal cord --namely the subarachnoid space--.The third model deals with the cardiovascular system. Cardiovascular diseases are the leading cause of death worldwide, among these diseases, thrombosis is a condition that involves the formation of a blood clot inside a blood vessel. A computational model that studies thrombus formation and evolution is developed, considering the chemical, bio-mechanical and fluid dynamical aspects of the problem in the same computational framework. In this model, the primary novelty is the introduction of the role of shear micro-gradients into the process of thrombogenesis.The developed models have provided several outcomes. First, the study of the fluid-structure interactions between cerebro-spinal fluid and the spinal cord has shed light on scenarios that may induce the occurrence of Syringomyelia. It was seen how the deviation from the physiological values of the Young modulus of the spinal cord, the capillary pressures at the SC-SAS interface and the permeability of blood networks can lead to syrinx formation.The computational model of the drug dispersion has allowed to quantitatively estimate the drug effective diffusivity, a feature that can aid the tuning of intrathecal delivery protocols.The comprehensive thrombus formation model has provided a quantification tool of the thrombotic deposition evolution in a blood vessel. In particular, the results have given insight into the importance of considering both mechanical and chemical activation and aggregation of platelets
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CARDILLO, GIULIA. "Fluid Dynamic Modeling of Biological Fluids: From the Cerebrospinal Fluid to Blood Thrombosis." Doctoral thesis, Politecnico di Torino, 2020. http://hdl.handle.net/11583/2845786.
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Lebret, Alain. "Study on the cerebrospinal fluid volumes." Thesis, Paris Est, 2013. http://www.theses.fr/2013PEST1088/document.
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Cette thèse contribue au manque d'outils informatiques pour l'analyse d'images médicales et le diagnostic, en particulier en ce qui concerne l'étude des volumes du liquide cérébrospinal. La première partie concerne la mesure du volume des compartiments du liquide à partir d'images corps entier, pour une population composée d'adultes sains et de patients atteints d'hydrocéphalie. Les images sont obtenues à partir d'une séquence IRM développée récemment et mettant en évidence le liquide par rapport aux structures voisines, de manière à faciliter sa segmentation. Nous proposons une méthode automatique de segmentation et de séparation des volumes permettant une quantification efficace et reproductible. Le ratio des volumes des compartiments sous-arachnoïdien et ventriculaire est constant chez l'adulte sain, ce qui permet de conserver une pression intracrânienne stable. En revanche, il diminue et varie fortement chez les patients atteints d'hydrocéphalie. Ce ratio fournit un index physiologique fiable pour l'aide au diagnostic de la maladie. La seconde partie de la thèse est consacrée à l'analyse de la distribution du liquide dans le compartiment sous-arachnoïdien intracrânial supérieur. Il convient de souligner que ce compartiment, particulièrement complexe d'un point de vue anatomique, demeure peu étudié. Nous proposons deux techniques de visualisation de la distribution du volume liquidien contenu dans ce compartiment, qui produisent des images bidimensionnelles à partir des images d'origine. Ces images permettent de caractériser la distribution du volume liquidien et de son réseau, tout en distinguant les adultes sains des patients souffrant d'hydrocéphalieThis work aims to contribute to the lack of computational methods for medical image analysis and diagnosis about the study of cerebrospinal fluid volumes. In the first part, we focus on the volume assessment of the fluid spaces, from whole body images, in a population consisting of healthy adults and hydrocephalus patients. To help segmentation, these images, obtained from a recent "tissue-specific" magnetic resonance imaging sequence, highlight cerebrospinal fluid unlike its neigh borhood structures. We propose automatic segmentation and separation methods of the different spaces, which allow efficient and reproducible quantification. We show that the ratio of the total subarachnoid space volume to the ventricular one is a proportionality constant for healthy adults, to support a stable intracranial pressure. However, this ratio decreases and varies significantly among patients suffering from hydrocephalus. This ratio provides a reliable physiological index to help in the diagnosis of hydrocephalus. The second part of this work is dedicated to the fluid volume distribution analysis within the superior cortical subarachnoid space. Anatomical complexity of this space induces that it remains poorly studied. We propose two complementary methods to visualize the fluid volume distribution, and which both produce two-dimensional images from the original ones. These images, called relief maps, are used to characterize respectively, the fluid volume distribution and the fluid network, to classify healthy adults and patients with hydrocephalus, and to perform patient monitoring before and after surgery
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Lebret, Alain, and Alain Lebret. "Study on the cerebrospinal fluid volumes." Phd thesis, Université Paris-Est, 2013. http://tel.archives-ouvertes.fr/tel-00939308.
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This work aims to contribute to the lack of computational methods for medical image analysis and diagnosis about the study of cerebrospinal fluid volumes. In the first part, we focus on the volume assessment of the fluid spaces, from whole body images, in a population consisting of healthy adults and hydrocephalus patients. To help segmentation, these images, obtained from a recent "tissue-specific" magnetic resonance imaging sequence, highlight cerebrospinal fluid unlike its neigh borhood structures. We propose automatic segmentation and separation methods of the different spaces, which allow efficient and reproducible quantification. We show that the ratio of the total subarachnoid space volume to the ventricular one is a proportionality constant for healthy adults, to support a stable intracranial pressure. However, this ratio decreases and varies significantly among patients suffering from hydrocephalus. This ratio provides a reliable physiological index to help in the diagnosis of hydrocephalus. The second part of this work is dedicated to the fluid volume distribution analysis within the superior cortical subarachnoid space. Anatomical complexity of this space induces that it remains poorly studied. We propose two complementary methods to visualize the fluid volume distribution, and which both produce two-dimensional images from the original ones. These images, called relief maps, are used to characterize respectively, the fluid volume distribution and the fluid network, to classify healthy adults and patients with hydrocephalus, and to perform patient monitoring before and after surgery
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Mohammed, Ben Husien. "Endoscopic repair of cerebrospinal fluid leaks." Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/27881.
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Developmental Venous Anomalies are a normal variant that may be associated with other cerebral vascular malformation they have bean previously referred to Venous angiomas. DVAs are the most frequently encountered cerebral vascular malformation and their incidence is reported to be high as 2.6%. DVAs are classified into two types based on draining veins. Either deep or superficial. Those that drain into subependymal veins are classified as deep and those that drain into cortical pial veins are classified as superficial. The trans-cerebral veins join either the deep or superficial venous systems by crossing a varying length of the brain parenchyma. Controversy surrounds their exact clinical significance, as DVAs are rarely symptomatic. The symptoms displayed by a patient can be related to a lesion that is associated with DVAs, such as a cavernoma. Study Aim: To describe the patients presenting to a single unit over a 10-year period with symptoms attributable to a DVA. Results: Out of 19 patients in the database with the diagnosis of DVA, 10 were identified where the clinical presentation was directly related to the DVA. Seven of the patients presented with haemorrhage, 6 had parenchymal bleeds and one was intraventricular. Two patients had neurological deficit, 1 was transient and one was progressive. One patient had sudden severe headache with no evidence of haemorrhage on CT scan. The age range was from 14 to 55 with a mean of 32,7 years. Four patients were male and 6 were female. Of the patients that presented with haemorrhage only one had a fistula, three other patients with haemorrhage had evidence on DSA of stenosis of the large collector vein, In the remaining 3 patients no reason for the bleed could be detected. One patient presented with left hemianopia that resolved after several hours, DSA showed minimal caput medusa with delayed filling of the collector vein. The other patient that presented with progressive neurological deficit in the form of progressive leg spasticity and dysarthria, Angiography showed a large collecting vein that drains in the jugular bulb was stenosed. The last patient that presented with sudden sever headaches, with no haemorrhage identified on CT scan, On DSA there was early filling of the DVA veins compared to other cerebral veins and two prominent posterior communicating thalamoperforating vessels were seen. Conclusion: Developmental venous anomalies are the commonest vascular malformation, and are rarely symptomatic unless associated with a cavernoma. In patients that have symptoms linked to DVAs (Haemorrhage, neurological deficit, sudden sever headaches) overall they have a good outcome, and the deficit related to a DVA tend to improve overtime, except for one patient that we had in our group, the DVA draining the pons and the cerebellar hemisphere had a tight outflow stenosis, that lead to progressive neurological deficit. In general, the majority of DVAs that are symptomatic do well.
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Kronander, Björn. "Quantification of alpha-synuclein in cerebrospinal fluid." Thesis, Linköpings universitet, Institutionen för fysik, kemi och biologi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-84598.
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To date there is no accepted clinical diagnostic test for Parkinson's disease (PD) based on biochemical analyses of blood or cerebrospinal uid. Currently, diagnosis, measurement of disease progression and response to therapeutic intervention are based on clinical observation, but the rst neuronal dysfunction precede the earliest recognition of symptom by at least 5 - 10 years. A potential diagnostic biomarker is oligomeric alpha-synuclein which in recent papers have reported a signicant quantitative dierence between PD and controls. In this master thesis, a method for measuring oligomeric levels of alpha-synuclein is presented together with a monomeric measuring commercial kit used to measure alpha-synuclein in a preclinical model of PD. A signicant dierence of monomeric levels could be detected between two weeks and four weeks post injection of a vector containing the gene for human alpha-synuclein, no signicant dierence between four and eight weeks was found.
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Saugstad, Julie A., Theresa A. Lusardi, Keuren-Jensen Kendall R. Van, Jay I. Phillips, Babett Lind, Christina A. Harrington, Trevor J. McFarland, et al. "Analysis of extracellular RNA in cerebrospinal fluid." TAYLOR & FRANCIS LTD, 2017. http://hdl.handle.net/10150/624656.
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We examined the extracellular vesicle (EV) and RNA composition of pooled normal cerebrospinal fluid (CSF) samples and CSF from five major neurological disorders: Alzheimer's disease (AD), Parkinson's disease (PD), low-grade glioma (LGG), glioblastoma multiforme (GBM), and subarachnoid haemorrhage (SAH), representing neurodegenerative disease, cancer, and severe acute brain injury. We evaluated: (I) size and quantity of EVs by nanoparticle tracking analysis (NTA) and vesicle flow cytometry (VFC), (II) RNA yield and purity using four RNA isolation kits, (III) replication of RNA yields within and between laboratories, and (IV) composition of total and EV RNAs by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and RNA sequencing (RNASeq). The CSF contained similar to 106 EVs/mu L by NTA and VFC. Brain tumour and SAH CSF contained more EVs and RNA relative to normal, AD, and PD. RT-qPCR and RNASeq identified disease-related populations of microRNAs and messenger RNAs (mRNAs) relative to normal CSF, in both total and EV fractions. This work presents relevant measures selected to inform the design of subsequent replicative CSF studies. The range of neurological diseases highlights variations in total and EV RNA content due to disease or collection site, revealing critical considerations guiding the selection of appropriate approaches and controls for CSF studies.
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Böhm, Urs Lucas. "Physiological inputs to cerebrospinal fluid-contacting neurons." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066196/document.
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Les neurones au contact du liquide céphalorachidien (CSF-cNs) sont des cellules ciliées présentes tout autour du canal central de la moelle épinière. Ces cellules sont GABAergiques, déploient une brosse de microvillosités à l'intérieur de la lumière du canal et sont caractérisées par une expression du canal ionique Pkd2l1. Ceci les désigne comme de potentielles cellules sensorielles. Il a été montré que les CSF-cNs peuvent moduler la locomotion et qu'elles réagissent aux variations de pH in vitro. Cependant les modalités sensorielles transmises par ces cellules et leur implication dans la fonction locomotrice nous échappent encore. Dans ma thèse, j'étudie la fonction sensorielle des CSF-cNs dans la moelle épinière de la larve de poisson zèbre. En combinant le relargage de proton et l'imagerie pH avec l'imagerie calcique, nous avons pu montrer que les CSF-cNs répondent à des pics d'acidification in vivo et que cette réponse persiste dans des mutants pkd2l1. Nous démontrons également que les CSF-cNs ne sont pas activés de façon coordonnée lors de la locomotion fictive. Les mouvements actifs ou passifs de la queue conduisent toutefois à l'activation spécifique des CSF-cNs ipsilatérales de la contraction musculaire. Ces observations suggèrent que les CSF-cNs sont recrutées par une stimulation mécanique. Les mutants pkd2l1 ont montré une diminution de la réponse à la flexion active et passive de la queue et une diminution de la fréquence de battement de la queue. Dans son ensemble, le travail présenté ici met donc en évidence que les CSF-cNs répondent aux variations de pH in vivo et révèle leur rôle d'organe mécanosensoriel permettant la modulation du réseau locomoteur spinalCerebrospinal fluid-contacting neurons (CSF-cNs) are ciliated cells surrounding the central canal. These cells are GABAergic, extend a brush of microvilli into the lumen and are specified by the expression of the transient receptor potential ion channel Pkd2l1. The atypical morphology of CSF-cNs and their location make them candidates for sensory cells. It has been shown that CSF-cNs modulate locomotion by projecting onto the locomotor central pattern generators (CPGs) and that CSF-cNs can react to changes of pH in vitro, but the sensory modality these cells convey to spinal circuits and their relevance to locomotion remain elusive. In my thesis I investigate the sensory function of CSF-cNs in the zebrafish larva spinal cord. By combining proton uncaging together with pH imaging and calcium imaging, we could show that CSF-cNs respond to pulses of acidification in vivo and that this response persists in pkd2l1 mutants. Using genetically encoded calcium sensors we showed that CSF-cNs are not coordinately activated during fictive locomotion. Active or passive tail movement, however, led to CSF-cN activation restrained to cells ipsilateral to muscle contraction. These observations suggest that CSF-cNs are recruited by ipsilateral muscle contraction and/or tail torsion. Pkd2l1 mutants showed a decreased response to active and passive bending of the tail and a subtle but consistent decrease of tail-beat frequency was observed in the startle response. Altogether, the presented work shows evidence that CSF-cNs respond to changes in CSF pH and reveals that CSF-cNs constitute a mechanosensory organ which operates during locomotion to modulate spinal CPGs
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Bozanovic-Sosic, Radenka. "Cerebrospinal fluid transport from the spinal subarachnoid compartment." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/MQ63094.pdf.
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Duque, Maria Carolina. "Immunophenotyping of blood and cerebrospinal fluid leukocytes in dogs." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ61893.pdf.
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Johnson, M. "A study of cerebrospinal fluid abnormalities in neurological disease." Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.371552.
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Silver, Ian M. F. "Hydraulic linkage between the cerebrospinal fluid compartment and cervical lymphatics." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ46050.pdf.
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Hansson, Sara. "Proteomic strategies for analysis of cerebrospinal fluid in neurodegenerative disorders /." Göteborg : Institute of Neuroscience and Physiology, Dept. of Psychiatry and Neurochemistry at Sahlgrenska Academy University of Gothenburgh, 2008. http://hdl.handle.net/2077/9904.
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Berg, Mascha Petronella van den. "Nasal drug delivery : a direct approach to the cerebrospinal fluid ? /." [S.l. : s.n], 2005. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=014944343&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
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Jones, Claire Frances. "Cerebrospinal fluid mechanics during and after experimental spinal cord injury." Thesis, University of British Columbia, 2011. http://hdl.handle.net/2429/35757.
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Despite concentrated research efforts there is currently no treatment for spinal cord injury (SCI). Several researchers have identified that cerebrospinal fluid (CSF) may have a role in the biomechanics of the injury event and in the secondary physiologic response, but this has not been closely examined. The aim of this thesis was to develop a large animal model and a benchtop model of human SCI, and to use these to characterise (1) the pressure response of the CSF during the SCI event, (2) the effect of CSF thickness on mechanical indicators of injury severity, and (3) the pressure differentials and cord morphology associated with thecal occlusion and decompression.
Study 1 presented the large animal model and provided preliminary CSF pressure transient data that indicated further investigation was warranted. In Study 2, the CSF pressure transients from medium and high severity human-like SCIs were characterised. The peak pressures at 30 mm from the impact were within the range associated with experimental traumatic brain injury, but the wave was damped to peak pressures associated with noninjurious everyday fluctuations by 100 mm. In Study 3, results from the bench-top model demonstrated that the thickness of the CSF layer is directly proportional to the resultant peak CSF pressure, cord compression and impact load.
In Study 4, the cranial-caudal CSF pressure differential increased gradually over eight hours of thecal occlusion. Decompression eliminated or reduced the differential, after which it did not change significantly. These results indicate that lumbar CSF pressure measured prior to decompression may not be representative of CSF pressure cranial to an injury. In Study 5, the change in spinal cord and thecal sac morphology after surgical decompression was assessed with ultrasound. Moderate SCI was associated with a residual cord deformation and then gradual swelling, while high severity SCIs exhibited immediate swelling which occluded the thecal sac within five hours.
The different aspects of CSF response to SCI demonstrated in this thesis can potentially be used to assess and validate current and future models of SCI, and to guide future studies of clinical management strategies such as CSF drainage and early decompression.
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Goonetilleke, Upali R. "Proteomics of cerebrospinal fluid in patients diagnosed with pneumococcal meningitis." Thesis, University of Liverpool, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.539528.
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Tully, Brett. "Allostasis of cerebral water : modelling the transport of cerebrospinal fluid." Thesis, University of Oxford, 2010. http://ora.ox.ac.uk/objects/uuid:168586f0-f34a-4d5e-8acf-822cd0e1bfe2.
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A validated model of water transport in the cerebral environment is both an ambitious and timely task; many brain diseases relate to imbalances in water regulation. From tumours to strokes, chronic or acute, transport of fluid in the brain plays a crucial role. The importance and complexity of the brain, together with the range of unmet clinical needs that are connected with this organ,make the current research a high-priority. One of the most paradoxical cerebral conditions, hydrocephalus, serves as an excellent metric for judging the success of anymodel developed. In particular, normal pressure hydrocephalus (NPH) is a paradoxical condition with no known cure and existing treatments display unacceptably high failure rates. NPH is considered to be a disease of old age, and like many such diseases, it is related to a change in the transport of fluid in the cerebral environment. This complex system ranges from organ-level transport to cellular membrane channels such as aquaporins; through integrating it in a novel mathematical framework, we suggest that the underlying logic of treatment methods may be misleading. By modelling the transport of cerebrospinal fluid (CSF) between the ventricular system, cerebral tissue and blood networks, we find that changes to the biophysical properties of the brain (rather than structural changes such as aqueduct obstruction) are capable of producing clinically relevant ventriculomegaly in the absence of any obstruction to CSF flowthrough the ventricular system. Specifically, the combination of increased leakiness and compliance of the capillary bed leads to the development of enlarged ventricles with a normal ventricular pressure, replicating clinical features of the presentation of NPH. These results, while needing experimental validation, imply that treatment methods like shunting, that are focussed on structural manipulation, may continue to fail at unacceptably high rates.
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Rogers, Stephen. "Glycosylation of immunoglobulin G in cerebrospinal fluid and multiple sclerosis." Thesis, University of Surrey, 2001. http://epubs.surrey.ac.uk/843781/.
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The glycosylation features of CSF oligoclonal IgG, and possible changes in N-glycans of CSF IgG in multiple sclerosis (MS) were studied. After isoelectric focusing (IEF) of CSF, bands were detected using biotinylated lectins and avidin-horseradish peroxidase. Concanavalin A (Con A) binding showed that mannose exists throughout the pH range of oligoclonal IgG. Sambucus nigra antigen (SNA) bound acidic and neutral oligoclonal IgG only, suggesting that alkaline oligoclonal IgG is deficient in sialic acid. Deglycosylation of CSF IgG using peptide-N-glycosidase F suggested that the range of isoelectric points of oligoclonal IgG bands is not due to carbohydrate differences alone. Lectin immunoassays, whereby protein A purified IgG was captured by anti-IgG coated tubes and probed using a range of biotinylated lectins, were used to compare 13 CSF samples from MS patients with 14 control samples. With Con A binding, a significantly higher mean and larger variance was found for the MS group (t-test: P < 0.05). Con A binding correlated with CSF [IgG]/[total protein]% (r=0.390; P=0.0443). Using HPLC to separate oligosaccharides released from IgG by hydrazinolysis and labelled with 2-aminobenzamide, glycans were determined in 7 CSF samples with oligoclonal IgG, and 6 CSF samples without. The ratio of the peak for biantennary fucosylated agalactosyl glycans to total monogalactosylated glycan peaks was lower for the oligoclonal IgG samples (t-test: P=0.0141). The overall results suggested that glycosylation changes occur in CSF IgG in MS, and that oligoclonal IgG contains less sialic acid but more galactose than polyclonal IgG.
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Djenoune, Lydia. "Molecular and morphological analysis and spinal cerebrospinal fluid-contacting neurons." Paris, Muséum national d'histoire naturelle, 2012. http://www.theses.fr/2015MNHN0018.
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Le liquide céphalorachidien (LCR) enveloppe l’intégralité du système nerveux central (SNC). Il assure le transport d’éléments permettant la modulation de l’activité du SNC. Ce phénomène suggère que des signaux du LCR pourraient agir sur des neurones du SNC via des cellules réceptrices bordantes. Dans la moelle épinière, les neurones candidats à cette fonction intégratrice sont les neurones contactant le liquide céphalorachidien (NcLCRs). L’extension apicale caractéristique des NcLCRs contient des microvillosités baignant dans le LCR suggérant des fonctions sensorielles et/ou sécrétrices. La description des NcLCRs dans plus de 200 vertébrés suggère une fonction majeure. Cependant, le manque de marqueurs spécifiques et la difficulté d’accéder aux NcLCRs ont ralenti l’étude de leur physiologie. Nos travaux ont permis l’identification de PKD2L1, un canal transient receptor potential, comme marqueur spécifique des NcLCRs médullaires du poisson-zèbre, de la souris et du macaque. Après avoir généré des lignées transgéniques de poisson-zèbre spécifiques des NcLCRs en clonant un promoteur minimal de pkd2l1, nous avons décrit l’hétérogénéité moléculaire et morphologique des NcLCRs tout comme leur niveau élevé d’activité calcique spontanée chez l’embryon restreinte aux NcLCRs ventraux. En générant des mutants de pkd2l1, nous avons montré que le canal portait cette activité aux stades précoces du développement et testé le rôle de cette activité dans la morphogenèse des NcLCRs. Dans leur ensemble, nos travaux caractérisent un répertoire de marqueurs moléculaires spécifiques ainsi que la morphologie des NcLCRsThe cerebrospinal fluid (CSF) is circulating around the entire central nervous system (CNS). It conveys signals modulating the activity of the nervous system. This phenomenon implies that cues from the CSF could act on neurons of the brain and the spinal cord via bordering receptor cells. In the spinal cord, candidate neurons to allow these functions are the cerebrospinal fluid-contacting neurons (CSF-cNs). The atypical apical bulbous dendritic extension of CSF-cNs bears a cluster of microvilli bathing in the CSF indicating putative sensory or secretory roles. The fact that CSF-cNs have been described in over two hundred vertebrates suggests an important function within the spinal cord. However, the lack of specific markers and the difficulty to access CSF-cNs hampered their physiological investigation. Here we identified PKD2L1, a transient receptor potential channel, as a specific marker of spinal CSF-cNs in zebrafish, mouse and macaque. Next we generated specific transgenic zebrafish lines targeting CSF-cNs by cloning a minimal pkd2l1 promoter. We took advantage of these stable transgenic lines to describe the molecular and morphological heterogeneity of CSF-cNs as well as the striking level of spontaneous embryonic calcium activity restricted to the ventral CSF-cNs. By generating pkd2l1 mutants using TALENs, we showed that pkd2l1 drives spontaneous calcium activity in CSF-cNs at early stages of development and we tested the role of this early activity on CSF-cN morphogenesis. Altogether our work characterized a repertoire of molecular markers and morphology of CSF-cNs by taking advantage of the transparency and genetic accessibility of zebrafish
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Bergman, Robert Loring. "Matrix Metalloproteinases 2 and 9 in Normal Canine Cerebrospinal Fluid." Thesis, Virginia Tech, 2001. http://hdl.handle.net/10919/33750.
Full textAbstract:
Cerebrospinal fluid (CSF) analysis is a standard part of a diagnostic evaluation. Commonly evaluated components include the cell count, protein concentration, glucose, and cytology. CSF analysis can be diagnostic in some diseases such as fungal infections and CNS lymphoma. Often, CSF analysis is not specific, but more information can be obtained. Matrix Metalloproteinases (MMPs) are enzymes that have been found in human CSF. They are calcium and zinc dependent endoproteinases with overlapping substrates. They hydrolyze at least one component of tissue extracellular matrix (ECM), such as collagen or elastin. They are important in normal physiologic processes such as angiogenesis, reproduction and wound healing. One class of MMPs, the gelatinases, degrade gelatins and type IV collagen include MMP 2 and MMP 9. MMPs are important in many pathological processes that involve unregulated matrix destruction such as arthritis, neoplasia and CNS diseases. MMP2 is known to be constituitively produced in CSF while MMP 9 is present only in certain pathologic conditions such as multiple sclerosis, neoplasia and inflammatory diseases. We hypothesize that MMP2 is present in normal canine CSF while MMP 9 is absent.
Cerebrospinal fluid samples were taken from 23 normal dogs that were being used for other research purposes. Each CSF sample was evaluated immediately for red blood cells (RBCs), white blood cells (WBCs), protein, and glucose, and then stored at -70°C. Cytological examination was also performed. CSF samples were considered normal if the protein was less than 25 mg/dl, WBCs were less than 6 µl, and RBCs were less than 25 µl. Each dog was euthanized and the brains processed for routine histopathology. MMP analysis was done using gelatin zymography and an enzyme linked immunosorbent assay (ELISA). Bands of enzyme activity were visible following staining due to enzyme degradation of the gelatin. A commercially available polyclonal sandwich ELISA was used to identify the pro form of MMP2.
The mean WBC count for the CSF samples was 0.96 WBC/ml with a range of 0-3 WBC/ml. The mean protein was 12 mg/dl, with a range of 8-17 mg/dl. The mean RBC count was 3.65 RBC/ml with a range of 0-21 RBC/ml. All normal samples of CSF contained a band of clearing that corresponded to the human commercial standard of proMMP2. No other major bands of clearing were noted on normal samples. The commercial human standards also contained ProMMP2. Other bands were present, but were faint and variable. Using a polyclonal antibody based sandwich ELISA, with samples run in triplicate, the mean pro MMP 2 levels were determined to be 5.61 ng/ml with a range of 3.36 - 10.83 ng/ml.
We conclude that normal CSF values are narrower than what has been previously reported for protein concentration and WBC count. Also, the pro form of MMP 2 is present in normal canine CSF based on results of gelatin zymography and ELISA.Master of Science
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Beggs, Clive Barron. "Venous haemodynamic and cerebrospinal fluid anomalies associated with multiple sclerosis." Thesis, University of Bradford, 2014. http://hdl.handle.net/10454/7321.
Full textAbstract:
This critical synopsis of prior work by Clive Beggs is submitted in support of a PhD by published work. The work focuses on venous and cerebrospinal fluid (CSF) anomalies associated with multiple sclerosis (MS) and other neurological diseases. MS is characterized by focal inflammatory lesions, which are often venocentric. Recently a vascular syndrome, chronic cerebrospinal venous insufficiency (CCSVI) has been linked with MS. This syndrome, which is characterized by constricted cerebral venous outflow, has become mired in controversy, with various studies producing conflicting findings, with the result that the science associated with CCSVI has become obscured. Clive Beggs work seeks to bring clarity to the debate surrounding CCSVI by characterizing physiological changes associated with constricted cerebral venous outflow. The work submitted here involves collaborative studies with Robert Zivadinov (University of Buffalo), Paolo Zamboni (University of Ferrara), and Chih- Ping Chung (National Yang Ming University of Medicine). The key findings of these studies are: (i) MS patients, diagnosed with CCSVI, exhibit greatly increased hydraulic resistance of the cerebral venous drainage system; (ii) MS patients experience loss of the small cerebral veins; (iii) MS patients exhibit reduced CSF bulk flow, consistent with mild venous hypertension; (iv) MS patients exhibit increased CSF pulsatility in the Aqueduct of Sylvius, which appears to be linked with mild venous hypertension associated with CCSVI; and (v) jugular venous reflux is associated with white matter and parenchymal volumetric changes in Alzheimer’s patients. Collectively, these findings suggest that extracranial venous anomalies are associated with changes in the intracranial physiology.
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Beggs, Clive B. "Venous haemodynamic and cerebrospinal fluid anomalies associated with multiple sclerosis." Thesis, University of Bradford, 2014. http://hdl.handle.net/10454/7321.
Full textAbstract:
This critical synopsis of prior work by Clive Beggs is submitted in support of a PhD
by published work. The work focuses on venous and cerebrospinal fluid (CSF)
anomalies associated with multiple sclerosis (MS) and other neurological diseases.
MS is characterized by focal inflammatory lesions, which are often venocentric.
Recently a vascular syndrome, chronic cerebrospinal venous insufficiency (CCSVI)
has been linked with MS. This syndrome, which is characterized by constricted
cerebral venous outflow, has become mired in controversy, with various studies
producing conflicting findings, with the result that the science associated with
CCSVI has become obscured.
Clive Beggs work seeks to bring clarity to the debate surrounding CCSVI by
characterizing physiological changes associated with constricted cerebral venous
outflow. The work submitted here involves collaborative studies with Robert
Zivadinov (University of Buffalo), Paolo Zamboni (University of Ferrara), and Chih-
Ping Chung (National Yang Ming University of Medicine). The key findings of these
studies are: (i) MS patients, diagnosed with CCSVI, exhibit greatly increased
hydraulic resistance of the cerebral venous drainage system; (ii) MS patients
experience loss of the small cerebral veins; (iii) MS patients exhibit reduced CSF
bulk flow, consistent with mild venous hypertension; (iv) MS patients exhibit
increased CSF pulsatility in the Aqueduct of Sylvius, which appears to be linked
with mild venous hypertension associated with CCSVI; and (v) jugular venous reflux
is associated with white matter and parenchymal volumetric changes in Alzheimer’s
patients. Collectively, these findings suggest that extracranial venous anomalies are
associated with changes in the intracranial physiology.
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Chamoun, Mario-Christofer. "An Alzheimer-type cerebrospinal fluid profile in early Parkinson's disease." Thesis, Umeå universitet, Institutionen för psykologi, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-167374.
Full textAbstract:
In recent years, several studies have discovered traces of Alzheimer's (AD) biomarkers in a large portion of patients with Parkinson's disease (PD), which have been associated with subsequent dementia (PDD). However, the manifestation of AD biomarkers in PD is not fully understood. At present, few studies have investigated how common AD biomarkers are in newly diagnosed and unmedicated patients with PD. This cross-sectional cohort study investigated whether AD biomarkers were present in unmedicated and newly diagnosed patients with PD and patients with PD and overlapping clinical symptoms (cognitive impairment, depression, olfactory dysfunction). Cerebrospinal fluid (CSF) levels of AD biomarkers Amyloid-β-42 (Aβ42), phosphorylated-tau (p-tau), and total-tau (t-tau) were assessed in 343 patients with the mean age of 68,69 (SD=9,60), including 31 healthy controls with the mean age of 68,90 (SD=5,64). The participants were recruited from The New Parkinson Patient in Umea (NYPUM & PARKNY). The results showed a significant difference in CSF AD biomarkers between patients with PD and healthy controls, but not in patients with PD and overlapping clinical symptoms. The results point to the presence of AD pathology in early PD; however, the presence of AD pathology could not be further strengthened by the clinical overlapping symptoms. More prospective studies on newly diagnosed patients with PD need to be carried out to investigate the prognostic values of the presence of AD pathology found in PD.
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Green, Alison Jane Ellen. "Brain-specific proteins in the diagnosis of dementia." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313354.
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Abdelhak, Ahmed [Verfasser]. "Primary progressive multiple sclerosis (PPMS) – cerebrospinal fluid (CSF) profile / Ahmed Abdelhak." Ulm : Universität Ulm, 2018. http://d-nb.info/1150780983/34.
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Zainy, Mohammed. "Hydrodynamic modelling of cerebrospinal fluid motion within the human ventricular system." Thesis, Nottingham Trent University, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272855.
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Shafie, Intan Nur Fatiha. "The establishment of potential cerebrospinal fluid biomarkers for canine degenerative myelopathy." Thesis, University of Glasgow, 2013. http://theses.gla.ac.uk/4292/.
Full textAbstract:
Canine degenerative myelopathy(DM) is a late onset neurodegenerative disease that primarily affects German Shepherd dog (GSD), though a number of other specific breeds are also affected. The underlying cause of the disorder remains elusive, though recent advances have implicated a mutation of superoxide dismutase 1(Sod1) in the aetiology, also implying DM is a potential orthologue of human amyotrophic lateral sclerosis. The identification of the Sod1 mutation raises the index of suspicion for an individual animal, however it is not specifically diagnostic as a proportion of dogs homozygous for the Sod1 mutation do not develop DM. Therefore, there is a clinical need for the development of specific biomarker(s) for DM to support genetic test. The aim of this study was to establish potential biomarkers for DM by exploring canine cerebrospinal fluid (CSF). A dual strategy was adopted;1) Evaluation of potential ALS biomarkers in DM CSF, 2) Identification of novel biomarker(s) in DM CSF. The cases selected in this project had a presumptive diagnosis of DM and were homozygous for Sod1 mutation. Preliminary characterisation by Western blot and mass spectrometry identified four protein candidates in DM CSF, comprised of cystatin C, transthyretin (dimeric and monomeric TTR), haptoglobin and clusterin. Since the validity of these putative biomarkers may be influenced by pre-analytical variables that may arise from the clinical environment, we therefore assessed the impact of three potential sample handling practices on these four proteins. The results from these experiments demonstrate that dimeric TTR and clusterin were affected by sample handling conditions. Therefore, an appropriate protocol for CSF sample handling was established. Western blot analyses indicated that clusterin is the most viable biomarker candidate for DM. Clusterin was significantly elevated in DM CSF when compared to a range of neurological conditions. The second potential candidate for DM biomarker is TTR, which is potentially reduced, an observation similar to those found in ALS CSF. The relationship of these proteins in the pathogenic mechanisms that underpin DM is unclear. However, based on observations on ALS, it is reasonable to speculate that their alterations are associated with a toxic gain of function of the mutant SOD1 protein. The successful characterisation of clusterin and TTR in DM CSF may therefore represent components of a panel of emerging biomarkers that may combine to distinguish DM in the clinic and provide further insights into the disease mechanisms.
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Ågren, Wilsson Aina. "On the pathophysiology of idiopathic adult hydrosephalus syndrome : energy metabolism, protein patterns, and intracranial pressure." Umeå : Univ, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-520.
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Hägglund, Jesper. "Simulated cerebrospinal fluid motion due to pulsatile arterial flow : Master Thesis Project." Thesis, Umeå universitet, Institutionen för fysik, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-182508.
Full textAbstract:
All organs, including the brain, need a pathway to remove neurotoxic extracellular proteins. In the brain this is called the glymphatic system. The glymphatic system works by exchanging proteins from interstitial fluids to cerebrospinal fluids. The extracellular proteins are then removed through the cerebrospinal fluid drains. The glymphatic system is believed to be driven by arterial pulsatility, cerebrospinal fluid production and respiration. Cerebrospinal fluids enters the brain alongside arteries. In this project, we investigate if a simulated pulsatile flow in a common carotid artery can drive cerebrospinal fluid flow running along the artery, using computational simulations of a linearly elastic and fluid-structure multiphysical model in COMSOL. Our simulations show that a heartbeat pulse increases the arterial radius of the common carotid artery by 6 %. Experimental data, assessed using 4D magnetic resonance imaging of a living human, show an increase of 13 %. Moreover, our results indicate that arterial displacement itself is not able to drive cerebrospinal fluid flow. Instead, it seems to create a back and forth flow that possibly could help with the protein exchange between the cerebrospinal and interstitial fluids. Overall, the results indicate that the COMSOL Multiphysics linearly elastic model is not ideal for approximations of soft non-linearly elastic solids, such as soft polydimethylsiloxane and artery walls work for stiffer materials. The long term aim is to simulate a part of the glymphatic system and the present work is a starting point to reach this goal. As the simulations in this work are simplified there are more things to test in the future. For example, using the same geometries a non-linear elastic model could be tested. The pulsatile waveform or the geometry could be made more complex. Furthermore the model could be scaled down to represent a penetrating artery in the brain instead of the common carotid artery.
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Said, Ahmed Degmo. "Quantitative determination of cerebrospinal fluid bilirubin on a high throughput chemistry analyzer." Thesis, Uppsala University, Department of Medical Biochemistry and Microbiology, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-110290.
Full textAbstract:
Background Subarachnoid hemorrhage is a condition with high rates of mortality and morbidity. The diagnosis requires an urgent cerebral computed tomography scan and also a lumbar puncture if the scan fails to demonstrate intracranial blood. In Sweden the cerebrospinal fluid (CSF) is analyzed by spectrophotometric scanning for the presence of hemoglobin and bilirubin. The aim of the study was to develop a quantitative diazo reagent based analysis of cerebrospinal fluid bilirubin as a replacement for spectrophotometric scanning.
Methods The CSF bilirubin assay on an Architect C8000 chemistry analyzer was compared with spectrophotometry using patient samples.
Results The method correlates with spectrophotometry, has a good linearity and precision.
Conclusions Quantitative bilirubin measurement offers shorter turnaround times, simplifies the interpretation of the results and reduces work load in comparison with spectrophotometry.
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Arnell, Kai. "Cerebrospinal Fluid Shunts in Children : Technical Considerations and Treatment of Certain Complications." Doctoral thesis, Uppsala University, Department of Surgical Sciences, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8295.
Full textAbstract:
Ventriculo-peritoneal shunting is the most commonly used method for the treatment of paediatric hydrocephalus. Despite improved shunts and surgical techniques there are still complications. This retrospective study focuses on diagnoses and treatment of shunt malfunction and infections. Cost/benefit of using an adjustable shunt was assessed. Two adjustable cerebrospinal fluid shunts and their compatible antisiphon devices were compared in-vitro.
In 21 of 46 children the standard shunt was changed to an adjustable one due to over-drainage. Adjustment of the shunt was performed in 73% of the children thereby avoiding surgery in several cases. This was a financial advantage.
Ascites or an abdominal pseudocyst without infection was detected in eight children due to resorption difficulties. A ventriculo-atrial shunt was inserted for a period of time. In three children it could successfully be reverted to a ventriculo-peritoneal.
In six children papilloedema was the only sign of shunt dysfunction. At revision the intracranial pressure ranged from 25 to 52 cm H2O. Fundoscopic examination in children older than 8 years may detect symptomless shunt malfunction.
During a 13-year period 39 shunt infections were diagnosed. Skin bacteria were found in 80%. Prolonged and anaerobic cultures increased the detection rate by more than one third. The intraventricular infections were treated with intraventricular and systemic antibiotics resulting in quick sterilisation. No relapses were encountered. In five older children with distal catheter infection Propionibacterium acne was found. These were treated with intravenous antibiotics and exchanging of the shunt system.
Strata NSCTM and Codman HakimTM worked according to the manufacturers except at the lowest setting. The resistance was below and in the lower range of the physiological one respectively. The antisiphon device of Strata shunt had to be placed in line with shunt to function properly.
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Kostesky, Trisha Ehren. "A study of potential sporadic amyotrophic lateral sclerosis biomarkers in cerebrospinal fluid." Thesis, University of British Columbia, 2011. http://hdl.handle.net/2429/35690.
Full textAbstract:
Sporadic Amyotrophic Lateral Sclerosis (sALS) is a debilitating and fatal neurodegenerative disease of unknown etiology. It currently has no biochemical marker to confirm a clinical diagnosis, and this has negative consequences for patients when it comes to initiating early medical intervention and participating in therapeutic trials. Valid biomarkers can be useful for diagnostic and prognostic indications as well as providing insight into disease pathogenesis and identifying targets for therapeutic interventions. Cerebrospinal fluid (CSF) may be a particularly valuable source of biomarkers because it is in close anatomical proximity to the brain and spinal cord, thus making it a better reflection of biochemical alterations resulting from neurodegenerative disease. This study examined the proteome profile of CSF from sALS patients and controls to identify candidate biomarkers that might aid in the diagnosis of sALS and possibly provide insight into disease pathogenesis. An antibody microarray technique was used to measure the expression levels of various cell signalling proteins in the CSF of sALS patients and healthy controls. The results identified a number of protein changes in sALS CSF, including a considerable decrease in the level of ephrin type-A receptor 1 tyrosine kinase (EphA1) relative to control CSF. Follow-up validation studies by Western blotting with CSF samples from a separate cohort of 19 sALS patients, 21 healthy controls and 10 neurological disease controls confirmed a statistically significant decrease in EphA1 levels. As a diagnostic test, EphA1 levels in CSF had a statistically significant ability to discriminate between sALS patients and controls. Receptor levels also had a positive correlation with age at onset of sALS symptoms, indicating that this potential biomarker may be capable of identifying people who are prone to an earlier onset of disease. The Eph family of tyrosine kinase receptors engage in complex bidirectional signalling that functions as a major form of contact-dependent communication between cells, and mediates a variety of cellular responses. As research begins to further elucidate these multifaceted signalling mechanisms, imbalances in Eph receptor functioning are increasingly implicated in a variety of pathologies in the central nervous system that are related to some of the major features of ALS.
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Bäckryd, Emmanuel. "The Cerebrospinal Fluid in Severe Pain Conditions : Clinical, Pharmacological and Proteomic Aspects." Doctoral thesis, Linköpings universitet, Avdelningen för samhällsmedicin, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-121494.
Full textAbstract:
The treatment of both cancer pain and non-cancer chronic pain is still suboptimal. The overall aim of this PhD thesis was to conduct translational pain research at the interface between clinical pain medicine and the field of human proteomics, using the practice of intrathecal analgesia at our institution as a starting point. Hence, the cerebrospinal fluid (CSF) is at the centre of the present dissertation, both as a target for infusing analgesics (Papers I and II – clinical and pharmacological aspects) and as an important biofluid for human biomarker studies (Papers III and IV – proteomic aspects). In Paper I, 28 cases of intrathecal analgesia in cancer patients were prospectively followed. Movement-evoked breakthrough pain remained a major clinical problem throughout the study month despite otherwise successful intrathecal analgesia (defined as good control of spontaneous resting pain paralleled by a marked decrease of concomitant systemic opioid doses). This study therefore illustrates the importance of considering not only spontaneous resting pain but also movement-evoked breakthrough pain. In Paper II, an expert-based algorithm for trialing the intrathecal analgesic ziconotide by bolus injections was evaluated in an open-label study of 23 patients with chronic neuropathic pain. We found few responders (13%) according to the strict criteria of the algorithm, but ziconotide bolus injection trialing seems feasible. The predictive power of ziconotide bolus trialing remains unclear, and the pharmacological profile of ziconotide (with very slow tissue penetration due to high hydrophilicity) calls the rationale for ziconotide bolus trialing into question. In Paper III, we found low levels of beta-endorphin in the CSF of chronic neuropathic pain patients (n=15) compared to healthy controls (n=19). We speculate that this might indicate dysfunctional top-down control of nociception. Substance P levels in the CSF did not differ by univariate statistics. In Paper IV, the CSF proteome of 11 patients with chronic neuropathic pain and 11 healthy controls was exploratively studied, combining gel-based proteomics with multivariate data analysis. After eliminating four proteins associated with age, 32 proteins were found to highly discriminate between groups. Among these, the seven proteins having the highest discriminatory power between patients and controls were: one isoform of angiotensinogen, two isoforms of alpha-1-antitrypsin, three isoforms of haptoglobin, and one isoform of pigment epithelium-derived factor. In conclusion, this PhD thesis demonstrates the fruitfulness of studying the CSF, both as a target for infusing analgesics and as a potential mirror of the neurobiological processes involved in pathological pain conditions. The thesis points to the need for more research into the mechanisms of different pain conditions, in order to hopefully achieve the vision of mechanism-based pain diagnoses.
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Paterson, R. W. "Cerebrospinal fluid biomarkers in Alzheimer's disease : from bedside to bench and back." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1542226/.
Full textAbstract:
Alzheimer’s disease (AD) is a progressive neurodegenerative disease that results in cognitive impairment and death. The pathological hallmarks are extracellular cortical amyloid plaques and intraneuronal tangles composed of hyperphosphorylated tau. Although environmental and genetic factors contribute to the development of AD, the sequence of pathophysiological events that lead to Alzheimer’s dementia is not yet completely clear. The clinical diagnosis of AD during life can be challenging and factors that explain clinical phenotypic heterogeneity and variability in rates of disease progression are not well understood. Biomarkers, objective measures of biological function, can be employed to support a clinical diagnosis of AD and may be abnormal before the onset of clinical symptoms. Imaging and cerebrospinal fluid biomarkers (CSF) are now incorporated into clinical and research diagnostic criteria. CSF, which is in direct contact with the brain, is a promising source of biomarkers and has the potential to differentiate AD from other neurodegenerative dementias, explain clinical heterogeneity within AD and elucidate the role of other pathobiological pathways. Ultimately CSF biomarkers might facilitate diagnosis of AD in its pre-clinical phase and allow for treatment responses to be measured. In this thesis CSF samples from clinical cohorts of individuals with AD, other neurodegenerative diseases and healthy controls are analysed using an extended panel of enzyme-linked immunosorbent assays (ELISA) and a novel mass spectrometry based assay. For the established CSF biomarkers, the practical issues related to collection, transportation and storage of CSF are investigated. Amyloid positron emission tomography (PET) imaging is investigated as a means of validating clinical cutpoints. An extended panel of established and emerging ELISAs is used to determine the diagnostic utility of biomarkers for differentiating AD from other neurodegenerative dementias and for explaining phenotypic heterogeneity within AD. The role of CSF biomarkers as predictors of disease progression is investigated employing robust measures of brain atrophy as surrogate measures of rates of neurodegeneration. Finally CSF samples are probed for new AD biomarkers using a novel mass spectrometry based assay. A number of practical conclusions are drawn from this work: aliquot storage volume is identified as an important confounder in measured CSF b-Amyloid concentration. CSF laboratory transportation methods are shown not to have a significant impact on measured biomarker concentration. Amyloid PET is a valuable means of validating clinical diagnostic cutpoints of core CSF biomarkers. Tau/Ab1-42 ratio, Ab40/42 ratio, P-tau and NFL emerge as having diagnostic utility for differentiating AD from other neurodegenerative diseases, and have high sensitivity and specificity for distinguishing AD from bvFTD, SD and healthy controls. Important differences in T-tau, P-tau and neurofilament light distinguish different AD atypical phenotypes and may help to elucidate underlying biological differences between these syndromes: individuals with the visual variant of AD (posterior cortical atrophy) have the lowest levels of CSF Tau and lowest rates of cognitive decline while the frontal executive cases have highest levels of NFL and highest rates of cognitive decline indicating more rapid neurodegeneration. Several novel biomarkers including trefoil factor 3 and several markers involved in vascular remodeling, amyloid processing and neuroinflammation are identified as predictors of increased atrophy rates in amyloid positive individuals suggesting possible independent mechanisms driving differing rates of neurodegeneration between individuals. Other novel AD biomarkers including malate dehydrogenase are identified as distinguishing AD from controls using a novel mass spectrometry based assay. Moreover, this assay demonstrates how mass spectrometry might be used for biomarker discovery and rapid development of a high throughput multiplexed clinical CSF assay. Taken together these results address some of the unanswered questions about how CSF should be collected, handled and stored to optimize analytical standardization, and how clinical results might be validated using amyloid PET. This work establishes the clinical utility of established biomarkers for differentiating AD from other neurodegenerative diseases and identifies established and novel biomarkers that might explain clinical heterogeneity and rates of progression between individuals. Finally a method for rapidly developing new biomarkers is tested and validated.
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Wang, Michelle J. "Predictive ability of cerebrospinal fluid biomarkers in diagnosing and evaluating Parkinson's disease." Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/92059.
Full textAbstract:
Thesis: M. Eng., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2014.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (page 31).
Currently, there are a variety of clinical assessments and rating scales used in the research and treatment of Parkinson's disease (PD). Despite the widespread use and reliance on these scales, they do not offer a uniform, objective measure. Many previous studies have indicated promising relationships between various biomarkers and Parkinsonian symptoms that could lead to objective measures by using statistical methods and providing p-values. However, we could not find any literature that uses machine learning or directly tests predictive value. The goal of this thesis was to determine whether or not cerebrospinal fluid (CSF) biomarker data could predict incidence of Parkinson's with a high degree of accuracy and differentiate between patients with varying levels of severity. We used various supervised machine learning algorithms on the Parkinson's Progression Markers Initiative (PPMI) baseline data set provided by the Michael J. Fox Foundation, and reported the percentage of patients correctly diagnosed by each algorithm on an isolated test data set. The best classifier averaged 69% accuracy in distinguishing human controls from PD patients. While this does indicate the presence of some predictive power, it is not clinically useful and we tentatively conclude a negative result. The data pertain to the CSF biomarkers available from PPMI at the end of October 2013.
by Michelle J. Wang.
M. Eng.
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Thompson, Janet. "Trace element analysis of cerebrospinal fluid by inductively coupled plasma-mass spectrometry." Thesis, University of Surrey, 1994. http://epubs.surrey.ac.uk/843891/.
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Inductively coupled plasma-mass spectrometry (ICP-MS) is a comparatively new technique which in the last few years has been increasingly used for the analysis of biological samples. The multi-element capabilities of ICP-MS have been demonstrated for the analysis of several biological fluids including serum, whole blood and urine. This thesis evaluates the use of ICP-MS for the routine trace element analysis of cerebrospinal fluid (CSF). Although it is possible to introduce CSF directly into the pneumatic nebulizer of the ICP-MS a wet digestion method, using nitric acid with microwave or water bath heating, has been assessed in view of the safety precautions required when handling CSF (Appendix I). International standard reference material NIST SRM-909 Human Serum was used to test the validity of this procedure. The results obtained were comparable to the certified data for the elements Ca, Cr, Cu, Fe and Mg. Additionally Rb and Zn results agreed with other literature values. Good recoveries (92 to 105%) were obtained for the addition of Ca, Cu, Fe, Mg, Rb, Sr and Zn to CSF. Other elements were below the detection limit in the non-spiked CSF. A preliminary study of 163 CSF samples, obtained from patients undergoing routine lumbar punctures, gave elemental concentrations within the literature range. For multi-element scan mode many of the elements lay below the detection limit: Cd, Co, Sc, Sn and V at concentrations less than 1 ng ml-1 and Hg less than 2 ng ml-1. The reported values for Ba, Cs, Pb and Sb were less than 1 ng ml-1. Elemental concentrations for Al, Cu, Rb, Sr and Zn were in the ng ml-1 range and Mg, P, Ca and Br in the mug ml-1 range. However, as a result of the lumbar puncture procedure only small sample volumes of CSF were obtained (from 0.4 - 1.5 ml). Thus two sample volumes were used in the analysis 0.2 and 1.0 ml. The 1.0 ml sample volumes gave significantly lower elemental concentrations at the 95% confidence limit than the 0.2 ml volumes for the elements Mg, P, Ca, Cu and Br. These differences were not attributable to sample heterogeneity or pipetting errors. As a result of this and due to the necessity of changing ICP-MS instruments during this study the analytical performance of the ICP-MS was assessed. Detection limits at the ng ml-1 level were obtained for most elements. The instrumental accuracy was checked by analyzing NIST SRM 1643b Trace Elements in Water which gave comparable results to the certified data for V, Cr, Mn, Co, Zn, Cu, Cd and Pb. A linear dynamic range from 1 ng ml-1 to 5 mug ml-1 was established for the elements analyzed. It was found that the analytical performance of ICP-MS was impaired by the introduction of matrix elements (Na, K, Ca, Mg, P and Br). Some spectral interferences were caused by the addition of these matrix elements, for example 40Ar23Na+ on 63Cu+. However, suppression and enhancement of the analyte signals were observed depending on instrument operating parameters, such as nebulizer flow rate (NFR). As a result of these studies the optimum NFR for analyzing biological fluids (such as CSF and serum) was determined to be between 700 and 950 ml min-1. Although this NFR range did not provide the maximum analyte signal particularly for the low mass analytes, it did limit the spectroscopic and non-spectroscopic interferences. Preliminary studies in synthetic solutions showed that it was possible to correct for the matrix interferences with internal standards of similar mass to the analyte element. Several methods for correcting spectroscopic interferences were attempted: internal standards; standard addition; sample dilution; isotope dilution mass spectrometry and matrix matched standards. No one method was successful for all elements. Several elements could be determined namely. Mg, Rb, Cu and Sr and others depending on instrument fluctuations, blank contamination levels and their level in a particular CSF sample. These determinations could not be thought of as routine as correction procedures for the data varied from day to day as a result of instrument instability and signal drift, perhaps caused by the sample matrix. This study highlights the difficulty of using pneumatic nebulizer ICP-MS for the routine multi-element analysis of CSF.
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Abu, Rumeileh Samir [Verfasser]. "Cerebrospinal fluid ubiquitin as a biomarker in neurological diseases / Samir Abu Rumeileh." Ulm : Universität Ulm, 2021. http://d-nb.info/1238690505/34.
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Abbruscato, Thomas John 1970. "Opioid peptide permeation across the blood-brain and blood-cerebrospinal fluid barriers." Diss., The University of Arizona, 1997. http://hdl.handle.net/10150/282429.
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The passage of peptides across the blood-brain or blood-cerebrospinal fluid barrier is extremely limited. Peptides can be hindered from entering the central nervous system due to the hydrophilic nature of peptides and their susceptibility to enzymatic degradation by various peptidases. This limitation can be overcome through chemical modifications of opioid peptides with the goal of increasing biological stability and blood-central nervous system permeation. In the present studies, an in vitro bovine brain microvessel endothelial cell model of the blood-brain barrier was characterized both functionally and enzymatically. This primary culture model was found to be reflective of the in vivo blood-brain barrier in reference to predicting a peptides relative lipophilicity. Bovine brain microvessel endothelial cells were also found to be quite active enzymatically as far as the peptidases known to be involved in the degradation of methionine enkephalin. The conformationally stable analog of methionine enkephalin, DPDPE, was also characterized for its ability to enter the CNS using the in situ brain perfusion technique. DPDPE was found to enter the brain by both saturable and non-saturable uptake mechanisms. Chlorohalogenation was also found to significantly improve the central nervous system entry as well as biological stability of a potent opioid agonist, biphalin. In addition, the mu-opioid receptor selective antagonist, CTAP, was also evaluated for its ability to enter the CNS. The amount of CTAP that crossed both the blood-brain and blood-cerebrospinal fluid barrier was quantitatively comparable to the mu-selective agonist, morphine. Biphalin was found to enter both spinal and supra-spinal sites that have been shown previously to express mu and delta opioid receptors. In situ brain perfusion experiments identified a saturable component that contributes to the brain entry of [¹²⁵125I-Tyr¹]biphalin. Further experiments revealed that [¹²⁵125I-Tyr¹]biphalin was entering the CNS by the large neutral amino acid transporter and not by the leucine enkephalin uptake system or DPDPE transport system. This research has provided important preliminary work for the characterization of peptide transport into the brain. The importance of using neuropharmaceutical drug delivery vectors in modern medicine needs attention for the evolution of successful drug design targeted for CNS entry.
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Pasvogel, Alice Eleanor. "Cerebrospinal fluid phospholipid and creatine kinase isoenzyme changes following traumatic brain injury." Diss., The University of Arizona, 1999. http://hdl.handle.net/10150/284010.
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Traumatic brain injury (TBI) is a leading cause of mortality and morbidity in young adults. With TBI, a cascade of events is initiated that leads to the degradation of the lipid bilayer of the cell membrane. The purpose of this study was to investigate central nervous system membrane damage following traumatic brain injury through biological (phospholipid and creatine kinase isoenzyme) and behavioral (Glasgow Coma Scale score and Survival Status) measures. The purpose was also to determine the relationship between the biological measures of injury and the behavioral assessment of neurological status. Ten patients participated in the study. The cerebrospinal fluid (CSF) samples from the ventricular catheter system and Glasgow Coma Scale (GCS) scores were obtained 2-3 times each day over 2 to 3 days. The phospholipids were extracted from the CSF samples with a 2 step procedure using Chloroform:Methanol. The phospholipid classes were separated using normal phase High Performance Liquid Chromatography with a Hexane:Isopropanol:Water gradient and quantified from calibration curves for each of the phospholipid classes: phosphatidylethanolamine, phosphatidylserine, phosphatidylcholine, sphingomyelin, and lysophosphatidylcholine. The creatine kinase isoenzyme (CK-BB) concentration was determined by electrophoresis. Data were analyzed using descriptive statistics, Spearman rank order correlation coefficient, and point biserial correlation. The concentration of phospholipids and CK-BB changed over time with the peak mean concentration for phosphatidylethanolamine, phosphatidylcholine, and sphingomyelin on day 4 after injury; for phosphatidylserine on day 2 after injury, and for lysophosphatidylcholine and CK- BB on day 1 after injury. There was a significant positive relationship between phospholipids and the GCS score on day 2 after injury and a significant negative relationship between phospholipids and the GCS score on day 6 after injury. There was a significant relationship between Survival Status and phospholipids on day 1 and day 4 after injury. There was a significant relationship between Survival Status and CK-BB on day 1 and day 2 after injury. Future studies are needed to test the relationship between acute measures of membrane damage and long term physical, cognitive, emotional and behavioral outcomes.
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Rossmeisl, John H. Jr. "Effects of Blood Contamination on Cerebrospinal Fluid Cell Counts, Protein, and D-dimer Concentrations." Thesis, Virginia Tech, 2003. http://hdl.handle.net/10919/31015.
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Cerebrospinal fluid analysis (CSF) is commonly performed in clinical neurology, and is a sensitive, but non-specific indicator of central nervous system (CNS) pathology. Blood contaminated CSF samples have the potential to adversely affect results of cytologic, serologic, microbiologic, and molecular biologic diagnostics. A clear consensus of the effects of blood contamination on CSF analysis could not be drawn following a review of the existing veterinary literature. Based on data from earlier reports, it was hypothesized that iatrogenic blood contamination of CSF would result in significant increases in both the CSF total protein (TP) concentration and nucleated cell count (WBC). As hypothesized, in vitro CSF blood contamination resulted in statistically significant (p < 0.01) linear increases in both the CSF TP and WBC with increasing RBC concentration in CSF from sixteen normal dogs. Although increases in TP and WBC are statistically significant, their clinical impact is negligible. Results of this study demonstrate that in normal dogs, the mean CSF TP concentration collected from the cerebellomedullary cistern, is lower than previously reported.
D-dimers are plasminolytic cleavage products formed by the cross-linkage of fibrin by Factor XIIIa. In humans, D-dimer analysis can be used to differentiate iatrogenic from pathologic CNS hemorrhage. An additional objective of this study was to determine if canine D-dimers could be assayed using commercially available latex agglutination (LA) and enzymatic immunoassay (EIA) kits in normal and diseased subjects. It was hypothesized that qualitative and quantitative determinations of blood and CSF D-dimer activities could be aid in the diagnosis of dogs with altered CNS and/or systemic coagulation.
D-dimers were able to be assayed in all subjects studied. D-dimer concentrations in CSF samples, when analyzed using a qualitative LA assay system, from healthy dogs with iatrogenically blood contaminated CSF were consistently negative. Quantitation of CSF D-dimer concentrations in normal dogs using an EIA assay resulted in lower values (mean 16.2 + 4.3 ng/ml; range, 0 to 54 ng/ml) than detected in the peripheral blood of dogs and humans (normal cutoff value < 250 ng/ml). These findings suggest that D-dimer formation does not occur in canine CSF freshly contaminated with blood.
Significantly (p < 0.001) higher mean blood D-dimer concentrations were present in dogs with systemic coagulation disorders (1,093.4 + 172.3 ng/ml; range, 0 to > 2,000 ng/ml) when compared to normal dogs (54.6 + 19.8 ng/ml; range, 0 to 190 ng/ml), when assayed with the EIA. When used as an adjunct in the diagnosis of systemic coagulation abnormalities, the EIA assay had an overall sensitivity of 92%, specificity of 100%, positive predictive value (PPV) of 100%, and negative predictive value (NPV) of 94%. When applied to the same dogs, the LA D-dimer was less sensitive and specific (sensitivity of 73%, specificity of 100%, PPV of 100%, and NPV of 80%) than the EIA.
Evidence of intrathecal fibrinolysis in the absence of systemic abnormalities was also demonstrated using CSF LA and EIA D-dimer assays in some dogs with a variety of infectious (Rocky mountain spotted fever), non-infectious inflammatory (granulomatous meningoencephalitis, steroid-responsive meningitis), traumatic (intervertebral disc disease, spinal fracture), and neoplastic (meningioma) diseases. When all dogs with CNS diseases were examined together, the mean EIA D-dimer concentration was significantly (p = 0.03) higher (511.6 + 279.8 ng/ml) than normal dogs (mean 16.2 + 4.3 ng/ml). Future studies will be required before the definitive role of D-dimer analysis can be defined in veterinary medicine.Master of Science
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Eklundh, Thomas. "Lumbar puncture in psychiatric research : on the impact of confounding factors on monoamine compounds in cerebrospinal fluid /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4490-3/.
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Whitehouse, Helen Eleri. "Methods to assess CSF dynamics and the mechanical properties of the cerebral mantel in hydrocephalus." Thesis, University of London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322325.
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Samuel, Madan. "Quantitative assessment of the tympanic membrane displacement test in children and adolescents with shunted hydrocephalus : reproducibility of tympanic membrane displacement test measurements in children with shunted hydrocephalus." Thesis, University of Southampton, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266378.
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Alcolea, Rodríguez Daniel A. "Cerebrospinal fluid biomarkers for the study of the pathophysiological pathways in Alzheimer’s disease." Doctoral thesis, Universitat Autònoma de Barcelona, 2015. http://hdl.handle.net/10803/377443.
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Esta tesis profundiza en el conocimiento de las enfermedades neurodegenerativas y, concretamente, en la enfermedad de Alzheimer tanto en sus fases sintomáticas como en la etapa preclínica (antes de que se manifiesten los síntomas). Esto es posible a través del estudio de biomarcadores en líquido cefalorraquídeo, que reflejan in vivo los cambios que tienen lugar en el cerebro desde fases muy iniciales de la enfermedad y que son el hilo argumental de esta tesis doctoral.
A modo de introducción, el capítulo 1 define el marco y el contexto general de esta tesis resumiendo el conocimiento acerca de la enfermedad de Alzheimer y los biomarcadores. En el capítulo 2 estudiamos la viabilidad de la punción lumbar, la incidencia de complicaciones relacionadas con esta técnica y los factores que se asocian con ellas con el fin de determinar el impacto de este procedimiento para el estudio de biomarcadores de líquido cefalorraquídeo en las enfermedades neurodegenerativas. En el capítulo 3, se analizan las diferencias patofisiológicas entre la enfermedad de Alzheimer esporádica y familiar. El estudio de biomarcadores en líquido cefalorraquídeo nos permite identificar in vivo algunas características que complementan la información sobre el procesamiento de la proteína precursora de amiloide obtenida en el estudio neuropatológico. En el capítulo 4 profundizamos en las diferencias en biomarcadores en líquido cefalorraquídeo entre distintas enfermedades neurodegenerativas que cursan con demencia en sus fases sintomáticas, y estudiamos la relación entre biomarcadores involucrados en distintos procesos fisiopatológicos. La extensión de este estudio a las fases preclínicas conforman el capítulo 5. Para ello, analizamos el mismo conjunto de biomarcadores en una extensa cohorte de participantes sin déficits cognitivos. El capítulo 6 analiza la relación entre uno estos biomarcadores, YKL-40, y el grosor cortical medido por resonancia magnética en las fases predemencia de la enfermedad de Alzheimer. Finalente, en el capítulo 7 se pone en perspectiva todo lo expuesto para argumentar las conclusiones finales y formular las futuras líneas de investigación derivadas de estos proyectos.
En resumen, en esta tesis doctoral utilizamos los biomarcadores en líquido cefalorraquídeo para estudiar la enfermedad de Alzheimer des de un punto de vista traslacional en todas sus fases (clínica y preclínica), y para establecer relaciones entre diferentes procesos fisiopatológicos. Este tipo de abordaje es esencial para obtener herramientas de diagnóstico más precisas, profundizar en el conocimiento de los procesos que tienen lugar en fases iniciales de la enfermedad y, potencialmente, identificar nuevas dianas terapéuticas.This thesis deepens in the knowledge of key aspects of neurodegenerative diseases, and more precisely in AD, both in symptomatic and preclinical stages. This is achieved through the study of CSF biomarkers that reflect in vivo the changes that take place in the brain very early in the disease process, and that are the central line of the thesis. As an introduction, Chapter 1 sets the framework and general context for this thesis by summarizing the current knowledge on the field of AD and biomarkers. In chapter 2, we assessed the feasibility of lumbar puncture, the incidence of complications and their associated factors so as to determine the impact of this procedure in the study of CSF biomarkers of AD. Chapter 3 analyzes the pathophysiological differences between sporadic and autosomal dominant AD. CSF biomarkers allowed us to identify in vivo some characteristics in the processing of the amyloid precursor protein that complement the information found in neuropathological studies. In chapter 4, we study the differences in CSF biomarkers between neurodegenerative diseases that cause dementia in their symptomatic stages. We chose markers related to different pathophysiological processes and studied their relationship. We extended this study to preclinical stages in chapter 5. For this aim, we analyzed the same set of biomarkers in a large cohort of cognitively normal participants. Chapter 6 studies the relationship between one of these biomarkers, YKL-40, and cortical thickness measured by MRI in predementia stages of AD. Lastly, in chapter 7 we provide a general discussion and formulate the concluding remarks and future perspectives. In summary, in this thesis we use CSF biomarkers to study AD from a translational perspective in both clinical and preclinical stages and to identify relationships between distinct pathophysiological pathways. This kind of approach is essential to stablish new accurate diagnostic tools, to learn about the processes in the early stages of the disease, and, potentially, to discover new therapeutic targets.
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Cains, Sarah. "Cerebrospinal fluid folate and the development of the cerebral cortex in congenital hydrocephalus." Thesis, University of Manchester, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.518429.
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Bradley, Victoria. "Determining sub-arachnoid haemorrhage in the clinical biochemistry laboratory utilising cerebrospinal fluid samples." Thesis, University of Portsmouth, 2013. https://researchportal.port.ac.uk/portal/en/theses/determining-subarachnoid-haemorrhage-in-the-clinical-biochemistry-laboratory-utilising-cerebrospinal-fluid-samples(b68c29d7-afbe-4e20-9c26-a293df652963).html.
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Introduction: Sub-arachnoid haemorrhage (SAH) occurs when cerebral artery ruptures and blood leaks out into the sub-arachnoid space. This is often a catastrophic event for the individual and morbidity and mortality rates are significantly influenced by early intervention. This makes the role of the clinical biochemistry laboratory in early diagnosis vitally important, as delays in diagnosis can have a major clinical impact. The cerebrospinal fluid (CSF) of healthy individuals is optically clear. It has, however, been recognised for over a century that it can become coloured (xanthochromia) following a cerebrovascular incident such as a SAH. This has made the main role of the clinical biochemistry laboratory in SAH diagnosis that of detecting xanthochromia in the CSF. The majority of laboratories which offer a xanthochromia screening service use the national guidelines that are based upon ultra-violet scanning spectrophotometry (350 nm to 600 nm). This analytical technique is not without its problems: it is subjective, has a possibility of inter-operator variability and due to the specialised nature of the test can take many hours or even days for a result to be issued. This project aimed to improve the current laboratory service by investigating: turnaround times, users opinions of the current service and potential alternative analytical methods. Methods: An audit of the current analytical provision was used to assess its effectiveness and in order to elucidate the service users’ perception. This was effected by a questionnaire that was distributed to service users across three different NHS Trusts in England and Wales. In an attempt to improve the laboratory service, alternatives to scanning spectrophotometry were investigated. These were selected through consideration of the nature of SAH i.e. blood is released into the subarachnoid space and the brain is damaged. Laboratory analysis therefore needed to focus on detecting the presence of blood and/or its breakdown products, any change in CSF constituents that arise as a direct consequence of blood being introduced in to the subarachnoid space or a specific analyte which would only be present if brain damage occurred. Investigation of current research into subarachnoid haemorrhage identified the following analytes as potential alternatives: CSF diazo bilirubin, CSF Ferritin, CSF protein S100 and serum protein S100. Results: The audit revealed the average turnaround time for reporting xanthochromia results to be 26 hours, with almost 20% of samples being reported as equivocal. The service user’s questionnaire revealed a general lack of awareness of current United Kingdom National External Quality Assurance Scheme (UKNEQAS) guidelines for the ‘Analysis of cerebrospinal fluid for bilirubin in suspected Subarachnoid haemorrhage’ and a lack of understanding regarding the timing of lumbar punctures. Additionally, one third of users felt that the turnaround time for results was inadequate. CSF protein S100 was found to be unsuitable due to the difficulty in achieving a suitable balance between sensitivity and specificity; at a cut-off of 0.40 μg/l sensitivity is 80% and specificity is 4%, at a cut-off of 1.60 μg/l sensitivity is 40% and specificity is 94%. Serum protein S100 was found to be unsuitable due to the difficulty in achieving a suitable balance between sensitivity and specificity at appropriate cut-offs (66 % and 73%, respectively, at a cut-off of 0.09 μg/l). When the CSF diazo bilirubin and CSF ferritin were compared to current laboratory practises using pre-defined criteria then CSF diazo bilirubin was found to be the analyte of choice to base new guidelines upon. CSF diazo bilirubin was then used as an initial ‘rule-out’ step in a new set of guidelines for the determination of SAH utilising CSF analysis. Conclusion: The new guidelines employ CSF diazo bilirubin analysis as a ‘rule-out’ step with all samples that are above the cut-off (300 nmol/l) being processed through the UKNEQAS guidelines. In order for the guidelines to be introduced and accepted, local training and education programmes for laboratory and clinical staff will need to be developed and implemented and they will need to be disseminated through publication of articles in journals relevant to both the clinical biochemistry community and requesting clinicians.
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Chandorkar, Gurudatt Ajay Melethil Srikumaran K. "Mechanisms of blood-brain and blood-cerebrospinal fluid transport of aluminum in rats." Diss., UMK access, 2006.
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Thesis (Ph. D.)--School of Pharmacy. University of Missouri--Kansas City, 2006."A dissertation in pharmaceutical sciences and pharmacology." Advisor: Srikumaran Melethil. Typescript. Vita. Title from "catalog record" of the print edition Description based on contents viewed Dec. 20, 2007. Includes bibliographical references (leaves 159-192). Online version of the print edition.
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Piechnik, Stefan K. "A mathematical and biophysical modelling of cerebral blood flow and cerebrospinal fluid dynamics." Thesis, University of Cambridge, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269226.
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