MS is a chronic demyelinating disease of the CNS that presents with debilitating symptoms in the later stages of disease progression and therefore a high demand for targeted disease-modifying treatments exists. In order to create effective treatments the causalities between the symptoms and pathological mechanisms of the disease need to be properly understood. One such area that remains poorly understood is the role of excess iron deposition in disease aetiology and progression. Literature has

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... hown excess iron deposition in the brains of those with MS. However, whether it is the concentration of excess deposition, the brain-specific regions of deposition, or even the method of iron deposition/metabolism that causes this excess deposition is not understood. This thesis presents a set of experiments that observe the possible role of iron on inflammatory oligodendrocyte pathology, from a macro-to a micro-level. First, the deposition pattern of iron in regards to gross anatomy in brains affected by MS is observed and quantified using MRI images as well as tissue samples. The data presented here suggests that both the severity and/or maturity of the lesion play a role in the level of excess and pattern of iron deposition. Second, a set of experiments are performed that manipulate a pathway crucial to iron homeostasis as well as a group of receptors implicated in the disease progression of MS (HO-1 and P2X respectively) to elucidate possible synergistic activity between them. The results suggest an association between the purinergic receptors and the HO-1 pathway. iii Preface This thesis contains both independent and collaborative work. No publications yet The research in this thesis was conducted under the supervision of Dr. Kathryn Todd. The research presented in Chapter Two was formulated together with the team of scientists who helped me along the way as well as on my own. The research presented here encompasses a wide degree of interests including both in-vitro and clinical studies. It has been through the collaboration with the Department of Medicine, the NRU, the NMHI, and Pathology team that inspired me to ask further questions. iv