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

Investigating the control of striatal dopamine neurotransmission by axonal Ca2+ channels and by striatal neuromodulators : insights for Parkinson's disease

Brimblecombe, Katherine January 2013 (has links)
Dopamine (OA) is a key striatal neuromodulator which is central to processes including action selection and reward-related learning. OA dysfunction is associated with a number of psychomotor disorders, most notably of which is Parkinson's disease (PO). This thesis uses fastscan cyclic voltammetry in acute mouse striatal slices to detect OA release at carbon fibre microelectrodes with subsecond temporal resolution, to investigate factors affecting the presynaptic control of OA release. In this thesis, I have investigated the roles of voltage dependent calcium channels (VOCCs) and the neuromodulator, substance P (SP), in the presynaptic control of OA, in the presence of nicotinic acetylcholine receptor (nAChR) blockade. This is because ACh has profound modulatory and driving effects on OA release, via activation of nAChRs on OA terminals. In CPu, blockers for N-, P/Q-, T- or L-type VOCCs (w-Conotoxin GVIA, w-Agatoxin IVA, NNC 55- 0396, isradipine) reduced OA release to varying degrees (N)P/Q>T>L). Furthermore, L-type function was eliminated by a~synuclein knockout. In NAc, only Nand P/Q-blockers modified OA 1 release (N)P/Q) and more weakly than in CPu. Frequency-specific effects of some VGCCs were reproduced by changes to extracellular Ca 2 + or release probability, consistent with Ca 2 + entry governing the relationship between OA release probability and its short-term plasticity. Finally I have shown that SP can directly modulate striatal OA release in a manner that depends on striosome-matrix location. To date there is much conflict in the literature on the role of SP in a number of striatal processes, this finding may help to resolve these conflicts and shed light on the little understood role ofthe striosome-matrix division of the striatum.

The detection of intracranial aneurysms by non-invasive imaging methods and the epidemiology of aneurysmal subarachnoid haemorrhage within the Scottish population

White, P. M. January 2004 (has links)
The aims of the research project, which led to the writing of this thesis were to: Examine whether non-invasive imaging methods could replace intra-arterial angiography (IADSA) in the detection of intracranial aneurysms by: a) systematically reviewing the literature; b) prospectively determining the accuracy of non-invasive imaging methods currently available to Scotland, including the effect of observer experience on diagnostic performance and the patient acceptability of the alternative imaging modalities. To establish the incidence of aneurysmal subarachnoid haemorrhage (SAH) in families by a national retrospective study of occurrences of SAH in a one year period in Scotland, in parallel with a follow-up study of the families of patients who were admitted to the Institute of Neurosciences with aneurysmal SAH a decade earlier. The thesis is divided into three parts: Part One: a) summarises the current understanding of the epidemiology and pathophysiology of intracranial aneurysms; b) an overview of cerebrovascular anatomy with reference to aneurysm formation; c) the modalities available for imaging intracranial aneurysms and the current knowledge about their diagnostic performance are considered; d) an overview of the methods available for the treatment of intracranial aneurysms; e) the concept of screening for unruptured intracranial aneurysms is discussed and placed in context by comparison to other screening programmes. Part Two: a) describes a systematic review of the non-invasive imaging of intracranial aneurysms. CT and MR angiography had similar accuracy compared to IADSA of ~90%. Data on Transcranial Doppler Sonography (TCDS) were scantly but indicated poorer performance. Detection of very small aneurysms (<3 mm diameter) was significantly poorer for the non-invasive tests; b) describes a prospective study of 200 patients examining CTA, MRA and TCDS vs IADSA in the detection of intracranial aneurysms. CTA and MRA had an accuracy (per subject) of 0.85. TCDS had similar accuracy per subject but poorer accuracy per aneurysm than CTA or MRA. Detection of aneurysms £5mm was significantly poorer than for those >5mm. Interobserver agreement was good for all modalities; c) combining TCDS with CTA or MRA improved the detection of aneurysms on a per subject basis. Non-invasive imaging tests, especially when used in combination, are reliable at detecting aneurysms >5mm; d) examines the effect of observer experience. Neuroradiologists were more consistent and had better agreement with IADSA than non-neuroradiologists. Small aneurysms and cavernous/terminal internal carotid aneurysms were poorly detected by all observers; e) assessment of patient preferences indicated that TCDS was preferred to the other non-invasive tests and CTA or MRA, with the differences being statistically significant.

A developmental factor in Schilder's disease : a clinico-anatomical study, from the developmental aspect, of three cases of subacute diffuse cerebral sclerosis, with a note about the demyelinating diseases generally, the developmental nervous disorders and the functional psychoses

McHarg, J. F. January 1959 (has links)
No description available.

Automaticity in Huntington's disease

Thompson, Jennifer Charlotte January 2009 (has links)
Huntington's disease (HD) is an inherited neurodegenerative disorder. An intriguing observation in the HD literature is that simple psychomotor tasks with low rather than high demands on attention and executive function are the most sensitive markers oflongitudinal chance in HD, and most consistently distinguish pre-manifest carriers of the HD mutation from non-carriers. It has been suggested that this reflects in HD a breakdown in the ability to execute simple tasks automatically. This hypothesis was explored in a series of studies that examined the performance of HD patients and pre-manifest carriers of the HD mutation on a variety of psychomotor tasks using dual-task and procedural learning paradigms. On a simple 'dual-task' paradigm, in which patients were required to perform a simple paced finger-tapping task with one or both hands, patients with early HD showed increased tapping variability and reported greater subjective difficulty for the bimanual 'dual-task' condition compared with controls, suggesting that the simple finger-tapping action was not executed automatically but rather, placed greater demands on HD patients than controls. On a visually cued reaching task in which stimuli were ordered in a highly simple, repeating sequence, HD patients showed slow and minimal motor-skill improvement and, despite extensive practice, failed to reach the level of rapid, efficient performance associated with skill automisation. In a further study it was shown that a subset of patients, who had greater cognitive impairment, failed to acquire any knowledge of the repeating sequence. It was suggested that, in these patients, the performance of the reaching task itself was so demanding that patients lacked the attentional resources required to abstract the sequential pattern. Subtle indications of a breakdown in automaticity could also be detected in premanifest carriers of the HD mutation (P-HD). On a paced finger-tapping task, P-HD participants exhibited greater performance variability, the degree of which was correlated with estimated proximity to disease onset. In a subset ofP-HD participants who were estimated to be close-to-onset, variability was greater still and was disproportionately increased by the performance of a secondary cognitive task, indicating impaired ability to execute the tapping task without directed attention. Taken together, the studies suggest that a breakdown in automaticity is a fundamental feature of HD, reflecting progressive striatal degeneration. The findings have implications for the understanding of attentional impairment in HD. If simple tasks cannot be automated then they will necessarily place greater demands on attentional resources in HD.

Interactions between alertness and spatial awareness

Dodds, C. January 2007 (has links)
Unilateral neglect, a common consequence of a stroke, involves a difficulty with detecting and responding to contralesional stimuli. It has been shown to be a heterogeneous syndrome, involving a cluster of deficits in both spatial and nonspatial functions. Studies have shown that patients with neglect can suffer from problems with sustained attention, spatial working memory, temporal processing, and alertness, as well as the more obvious deficits in spatial orienting. One of the most intriguing features of neglect is the widely observed hemisphere lateralisation of the disorder. Neglect is more common, and more persistent, after right hemisphere lesions. Attempts to explain this lateralisation have generally focussed on hemispheric differences in the control of spatial attention. Kinsbourne (1987), for example, suggests that the right hemisphere controls the ability to orient attention to both sides of space, whilst the left hemisphere is only able to orient attention to the right side of space. An alternative theory is that the right hemisphere is specialised for the control of certain <i>nonspatial </i>functions, and it is the presence of deficits in these right hemisphere-lateralised functions which exacerbates spatial orienting in patients with unilateral neglect. This thesis explores this latter hypothesis and its implications, using a variety of techniques, including psychophysiology, neuropsychology, functional neuroimaging, and psychopharmacology. The central hypothesis of the thesis is that there is a direct link between nonspatial factors and spatial awareness, such that declining alertness or reduced cognitive resources may be sufficient to induce a rightward shift in spatial bias.

The development of TrkA binders : towards a novel Alzheimer's therapeutic

Hemmings, Jennifer L. January 2011 (has links)
This work is part of a wider ongoing collaborative program, involving expertise from within the University of Bristol. It has predominantly involved the development of novel small molecules with the potential to treat Alzheimer's disease, by targeting the extracellular domain of the kinase receptor, TrkA. TrkA binders can act as agonists, with the possibility to treat Alzheimer's disease or as antagonists with the ability to treat inflammatory pain. A novel family of antagonist compounds, based around methoxyphenyl 25 have been synthesised. This parent compound was prepared using reductive amination and had an ICso value of 20 IlM on an in-house radioligand competition binding assay. The lH_1SN HSQC protein NMR spectra of 25 with the TrkA protein showed peak shifts which indicate binding to the same region as the endogenous ligand (nerve growth factor).

A neurophysiologically plausible model for the origin of beta oscillations in Parkinson's Disease

Pavlides, Alex P. January 2013 (has links)
Parkinson's disease is one of the most common neurodegenerative diseases, yet despite its pervasiveness the underlying neural mechanisms of its onset and progression are still the subject of debate. One of the most important biomarkers of Parkinson 's disease is the occurrence of excessive oscillations in the beta frequency range 10 - 30Hz (dependent on species). These oscillations are found to be elevated in the basal ganglia, particularly within the subthalamic nucleus (STN) and globus pallidus external (GPe) in particular. Furthermore, the power of excessive beta oscillations is correlated with the symptoms of bradykinesia (slowness of movement) and muscle rigidity. A theoretical study by Holgado et al. (2010) has shown that the loop formed between the STN and GP can oscillate in the beta frequency range. In addition they identified the conditions under which this circuit could generate beta oscillations. This Thesis contributes to the field by first extending this analysis by deriving improved analytic stability conditions for realistic values of the synaptic transmission delay between STN and GP neurons. The improved conditions were significantly closer to the results of simulations for the range of synaptic transmission delays measured experimentally. Furthermore, the analysis explained how changes in cortical and striatal input to the STN-GP network influenced oscillations generated by the circuit. Despite the success of the model at reproducing a significant amount of experimental data it did not explain a number of additional experimental results: 1) The coherence of synchronous oscillations between STN and Cortex, and 2) evidence that lesion or DBS outside the STN-GP nuclei could also affect the power of the synchronous oscillations. To address this data, the model was extended to include the dependence of cortical input to STN on the feedback provided by the STN itself. This feedback was via the output nuclei (globus pallidus internal) , thalamus and so called hyperdirect pathway. It was found from an analysis of this model that feedback can enhance the STN-GP's propensity to oscillate. In addition, this model of beta oscillation generation was found to reproduce experimental data by Tachibana et al. (2011), such as the effects of blocking connections on oscillations, in a way that is distinct and differentiable from other models of beta Dscillation generation.

Biochemical investigation into problems relating to epilepsy

Halliday, J. January 1975 (has links)
No description available.

Studies on conduction in demyelinated peripheral nerves of the guinea-pig

Hall, J. I. January 1965 (has links)
No description available.

Studies of cerebral palsy in the childhood population of Edinburgh

Ingram, T. T. S. January 1961 (has links)
No description available.

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