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Assessing Midbrain Abnormalities In Parkinson’S Disease Using Magnetic Resonance Imaging, Kiarash Ghassaban

Wayne State University Dissertations

Diagnosing early-stage Parkinson’s disease (PD) and its manifestations is still a clinical challenge. Previous imaging studies using iron, neuromelanin (NM) and the Nigrosome-1 (N1) measures in the substantia nigra (SN) by themselves have been unable to provide sufficiently high diagnostic performance for these methods to be adopted clinically. In this dissertation, we start by studying idiopathic PD patients at their intermediate stages of the disease to evaluate the role of global and regional iron in the major deep gray matter nuclei. Then, we only focus on the NM complex in the midbrain and how neuronal loss interact with iron overload …

Reactions Of First-Row Transition Metal Complexes In Bis(Alkoxide) Ligand Environments With Diazoalkanes: Formation Of Carbenes Versus Reductive Coupling To Form Bridging Tetrazenes, Amanda Grass

Wayne State University Dissertations

This dissertation focuses on the design and reactions of novel late transition metal carbene complexes featuring alkoxide ligand environments. The high-valent cobalt carbene Co(OR)2(=CPh2) (OR = OCtBu2Ph), featuring short Co=C bond of 1.773(3) Å, was previously reported from the reaction of Co(OR)2(THF)2 with diphenyldiazoalkane. Magnetic and spectroscopic (EPR) studies demonstrated Co(OR)2(=CPh2) to be a low-spin S = ½ complex. Computational studies, in agreement with experimental data, suggested that the electronic structure of Co(OR)2(=CPh2) lies between intermediate spin Co(III) anti-ferromagnetically coupled to a carbene radical and a Co(IV) alkylidene. This dissertation began with investigation of this complex in carbene transfer reactivity. …

Measuring Brain Iron In Healthy Controls And Accessing Venous Abnormalities In Parkinson's Disease Using Mri, Manju Liu

Wayne State University Dissertations

Iron plays a key role in a number of brain cellular processes. However, abnormal brain iron regulation correlates with a number of neurodegenerative diseases such as Parkinson's disease, multiple sclerosis and so forth. To further elucidate the involvement of iron in neurodegenerative disorders, a robust in vivo quantitative non-invasive assessment of normal brain iron deposition over time is essential. A variety of magnetic resonance imaging (MRI) methods have been used to quantify iron both in vivo and in vitro non-invasively. We first created the baseline of phase value and ∆R2^* as a function of age in seven gray matter nuclei. …

Accumulation Of Subcortical Iron As A Modifier Of Volumetric And Cognitive Decline In Healthy Aging: Two Longitudinal Studies, Ana Marie Daugherty

Wayne State University Dissertations

Accumulation of non-heme iron in the brain has been theorized as a cellular mechanism underlying global neural and cognitive decline in normal aging and neurodegenerative disease. Relatively few studies of brain iron in normal aging exist and extant studies are almost exclusively cross-sectional. Here, I estimated iron content via T2* and measured volumes in several brain regions in two independent samples of healthy adults. The first sample (N = 89) was measured twice with a two-year delay; and the second sample (N = 32) was assessed four times over a span of 7 years. Latent models estimated change in iron …

Imaging Iron Content In Patients With Multiple Sclerosis Using Magnetic Resonance Imaging, Charbel Abdo Habib

Wayne State University Dissertations

The importance of iron in maintaining normal physiological processes in the human body has been well emphasized in the literature. However, "when iron behaves badly", its abnormal presence might lead to a spectrum of pathologies depending on what function has been altered. In the brain, for instance, abnormal iron content is thought to be associated with neurodegenerative diseases. In this dissertation, we study iron involvement in one of the most debilitating neurological diseases, multiple sclerosis (MS), using in vivo magnetic resonance imaging. We first test the sensitivity and specificity of the MR method used, known as susceptibility weighted imaging (SWI) …

The Role Of Cardiolipin In Iron Homeostasis And Glutathione Metabolism, Vinay A. Patil

Wayne State University Dissertations

Cardiolipin (CL) is the signature phospholipid of mitochondrial membranes, where it is synthesized locally and plays a critical role in mitochondrial bioenergetic functions. Inside the mitochondria, CL is a critical target of mitochondrial generated reactive oxygen species (ROS) and regulates signaling events related to apoptosis and aging. CL deficiency causes perturbation of signaling pathways outside the mitochondria, including the PKC-Slt2 cell integrity pathway and the high osmolarity glycerol (HOG) pathway, and is a key player in the cross-talk between the mitochondria and the vacuole. The importance of CL in human health is underscored by the observation that perturbation of CL …

Molecular Details Of The Mitochondrial Iron Sulfur Cluster Assembly Pathway, Swati Rawat

Wayne State University Dissertations

MOLECULAR DETAILS OF THE MITOCHONDRIAL IRON SULFUR CLUSTER ASSEMBLY PATHWAY

Iron-sulfur clusters are an important class of prosthetic group involved in electron transfer, enzyme catalysis, and regulation of gene expression. Their biosynthesis requires complex machinery located within the mitochondrion since free iron and sulfide are extremely toxic to the cell. Defects in this pathway results in several diseases such as Friedreich's Ataxia (FRDA), Sideroblastic Anemia and ISCU Myopathy. Therefore molecular details of the biogenesis pathway will provide deep insight in the pathway and treatment options for these diseases. FRDA is caused by deficiency of a single protein called as `Frataxin'. …