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Title: A physiological and pharmacological characterisation of spreading depression in the feline brain using magnetic resonance imaging
Author: Bradley, D. P.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2003
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Apparent diffusion coefficient (ADC) measurements can be mapped over the feline cerebral cortex using diffusion-weighted echo planar imaging (DW-EPI). These were used to visualise and quantify the propagation of DS events and characterise their associated ADC changes. The present study established for the first time that the characteristics of SD are profoundly affected by the nature of its initiating stimulus. Thus, a sustained stimulus produced permanent MRI intensity changes local to the site of stimulus application. It initiated a single primary followed by multiple secondary SD events. All their ADC deflection amplitudes were similar and conserved throughout the course of their propagation across the cortex. The secondary events were separated by similar time intervals but propagated with lower velocities than the primary SD events. In contrast, a transient stimulus did not produce any permanent MRI changes in parallel with expectations following migraine aura. It initiated fewer events although SD activity nevertheless persisted well after stimulus withdrawal consistent with expectations from a regenerative process. Furthermore, ADC deflections produce by the primary SD events progressively declined with their propagation. The secondary SD events produced significantly smaller ADC deflections separated by progressively larger time intervals, but had propagation velocities similar to their preceding primary SD events. The effect on SD events of the 5-hydroxytryptamine [5-HT1B/1D] agonist sumatriptan an agent established for the management of migraine and the novel benzoylamino benzopyran compound tonabersat were then compared. MRI made it possible to examine separately the actions of these compounds on the spatial extent and temporal characteristics of SD. Both compounds reduced the area affected by the primary SD event and the total period of SD activity. However, sumatriptan increased the number of SD events crossing the suprasylvian sulcus. In contrast, tonabersat reduced the frequency of SD events and in one case blocked all SD activity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available