30/01/2006 to 02/01/2009
cause of MS,
King’s College London
Prof. K.J. Smith
MS results in intense inflammation within the brain and spinal cord, and there is increasing evidence that this can directly cause conduction and neurological deficits. This PhD project explores the hypothesis that the deficits arise because the nerve fibres passing through inflammatory lesions are relatively starved of oxygen and glucose. The hypothesis is strongly supported by historical evidence, currently largely forgotten, that drugs that open blood vessels (e.g. amyl nitrite) can restore function in MS within an hour. This study proposes to explore the mechanisms underlying such phenomena using several different experimental inflammatory and/or demyelinating models, focusing on the oxygen concentration within the lesions. First, the distribution of oxygen within the lesion will be mapped using electrophysiological and morphological methods. Second, the oxygen supply to lesions will be modulated while observing the consequences on both the oxygen concentration within the lesion, and on the success of axonal conduction through the lesion. In addition, the oxygen and nutrient demand within the lesion will be increased by repetitive electrical stimulation, and the ability of the lesion and its vascular supply to maintain oxygen homeostasis will be determined. Finally, the functional consequences of manipulating blood flow and/or oxygen concentrations in experimental models will also be determined, to explore the feasibility of using modern drugs to develop a new symptomatic therapy for MS.
Maybe those in the UK could contact:
Professor Kenneth Smith
Professor Kenneth Smith is Professor of Neurophysiology at Department of Neuroimmunology, King’s College, London.