Publications by authors named "John Shelestak"

Unlabelled: Complex neurodevelopmental disorders involve motor as well as cognitive dysfunction and these impairments are associated with both cerebral and cerebellar maturity. A network of connections between these two brain regions is proposed to underlie neurodevelopmental impairments. The cerebellar gray matter has a protracted developmental timeline compared to the cerebral cortex, however, making the association of these relay pathways unclear for neurodevelopmental disabilities.

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Multiple sclerosis (MS) is initially characterized by myelin and axonal damage in central nervous system white matter lesions, but their causal role in synapse loss remains undefined. Gray matter atrophy is also present early in MS, making it unclear if synaptic alterations are driven by white matter demyelinating lesions or primary gray matter damage. Furthermore, whether axonal pathology occurs secondary to or independent of demyelination to drive synaptic changes is not clear.

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Glial cells, including astrocytes, microglia, and oligodendrocytes, are brain cells that support and dynamically interact with neurons and each other. These intercellular dynamics undergo changes during stress and disease states. In response to most forms of stress, astrocytes will undergo some variation of activation, meaning upregulation in certain proteins expressed and secreted and either upregulations or downregulations to various constitutive and normal functions.

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Multiple sclerosis (MS) is a neuroinflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). Immunomodulatory therapies are effective in reducing relapses, however, there is no remedy for progressive disease emphasizing the need for regenerative strategies. Chronic demyelination causes axonal injury and loss which is a key component of neurodegeneration and permanent disability in MS.

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The lack of acid stability in the stomach and of temporal stability when moving through the gastrointestinal (GI) tract has made the development of oral magnetic resonance imaging (MRI) contrast agents based on the platform of Gd -complexes problematic.On the other hand, the negative contrast enhancement produced by the T -weighted magnetic metal oxide nanoparticles (NPs) often renders the image readout difficult. Biocompatible NPs of the manganese Prussian blue analog K Mn [Fe (CN) ] exhibit extremely high stability under the acidic conditions of the gastric juice.

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The cuprizone induced animal model of demyelination is characterized by demyelination in many regions of the brain with high levels of demyelination in the corpus callosum as well as changes in neuronal function by 4-6 weeks of exposure. The model is used as a tool to study demyelination and subsequent degeneration as well as therapeutic interventions on these effects. Historically, the cuprizone model has been shown to contain no alterations to blood-brain barrier integrity, a key feature in many diseases that affect the central nervous system.

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Insult to the central nervous system (CNS) results in an early inflammatory response, which can be exploited as an initial indicator of neurological dysfunction. Nanoparticle drug delivery systems provide a mechanism to increase the uptake of drugs into specific cell types in the CNS such as microglia, the resident macrophage responsible for innate immune response. In this study, we developed two nanoparticle-based carriers as potential theranostic systems for drug delivery to microglial cells.

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Methionine metabolism is dysregulated in multiple sclerosis (MS). The methyl donor betaine is depleted in the MS brain where it is linked to changes in levels of histone H3 trimethylated on lysine 4 (H3K4me3) and mitochondrial impairment. We investigated the effects of replacing this depleted betaine in the cuprizone mouse model of MS.

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