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Title: An investigation into the role of remyelination failure as a contributing cause of axonal degeneration in the CNS
Author: Irvine, K. A.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2005
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Chapter 1 of the thesis reviews axonal degeneration in MS and the several mechanisms thought to contribute to axonal degeneration therein. Analyses of models of primary demyelination indicated that cuprizone intoxication combined with 40 Grays of X-irradiation to inhibit remyelination would provide a suitable model in which to test the proposed hypothesis. Chapter 2 presents the materials and methods used in this thesis. Chapter 3 first reviews the literature on cuprizone intoxication and then describes the consequences of combining X-irradiation with cuprizone intoxication in old mice. The results revealed that X-irradiation during cuprizone intoxication inhibited remyelination and resulted in an enhancement of axonal loss within the demyelinated corpus callosum. Unexpectedly, because it had not been reported previously, the non-irradiated mice, which were capable of remyelination, demonstrated significant axonal loss. Therefore in chapter 4 the extent of axon loss was examined in younger mice and compared with than which developed in old mice. To rule out a direct effect of X-irradiation on axons, chapter 5 reports the effect of exposing the brains of normal mice to the dose of X-irradiation used to inhibit remyelination. Chapter 6 describes a transplantation study designed to separate the role of remyelination failure from altered glial cell responses as contributing factors to the axon degeneration observed in the old X-irradiated mice in chapter. The general discussion in chapter 7 of the thesis concludes that although the thesis does present evidence indicating that failed or slow remyelination contributes to the incidence of axonal degeneration, it is not yet possible to decide to what extent remyelination failure per se is the major contributor to the axon degeneration seen in the old mice. The relevance of the increase in axonal degeneration with age for MS is discussed. An influence of the strain of mouse to susceptibility to axonal degeneration during cuprizone is proposed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available