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Physiological Dynamics in Demyelinating Diseases: Unraveling Complex Relationships through Computer Modeling

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TLDR
This work will discuss how computational modeling applied to questions at different biological levels can help link together disparate observations and decipher complex mechanisms whose solutions are not amenable to simple reductionism.
Abstract
Despite intense research, few treatments are available for most neurological disorders. Demyelinating diseases are no exception. This is perhaps not surprising considering the multifactorial nature of these diseases, which involve complex interactions between immune system cells, glia and neurons. In the case of multiple sclerosis, for example, there is no unanimity among researchers about the cause or even which system or cell type could be ground zero. This situation precludes the development and strategic application of mechanism-based therapies. We will discuss how computational modeling applied to questions at different biological levels can help link together disparate observations and decipher complex mechanisms whose solutions are not amenable to simple reductionism. By making testable predictions and revealing critical gaps in existing knowledge, such models can help direct research and will provide a rigorous framework in which to integrate new data as they are collected. Nowadays, there is no shortage of data; the challenge is to make sense of it all. In that respect, computational modeling is an invaluable tool that could, ultimately, transform how we understand, diagnose, and treat demyelinating diseases.

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Journal ArticleDOI

Four in vivo g‐ratio‐weighted imaging methods: Comparability and repeatability at the group level

TL;DR: The data showed that repeatability and comparability depend largely on the marker for the FVF (NODDI outperformed TFD), and that they were improved by masking, and that the calibration procedure is crucial, for example, calibration to a lower g‐ratio value than the commonly used one.
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Towards in vivo g-ratio mapping using MRI: Unifying myelin and diffusion imaging.

TL;DR: In this paper, the authors present a review of the most recent developments in the field, while also providing methodological background pertinent to aggregate g-ratio weighted mapping, and discussing pitfalls associated with these approaches.
Posted Content

Towards in vivo g-ratio mapping using MRI: unifying myelin and diffusion imaging

TL;DR: A second review on the topic of g-ratio mapping using MRI with a summary of the most recent developments in the field providing methodological background is published.
Journal ArticleDOI

Iron Oxide Nanoparticles Affects Behaviour and Monoamine Levels in Mice

TL;DR: Over expression of glial fibrillary acidic protein (GFAP) confirms the neuronal damage, suggesting the evidences for behavioural changes, and mitochondrial damage, depleted energy level and decreased ATPase activities were observed in mice exposed to Fe2O3-NPs.
References
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Journal ArticleDOI

Proposed evolutionary changes in the role of myelin

TL;DR: The hypothesis is that the main purpose of myelin changed from energy conservation to conduction speed increase during this Mesozoic marine revolution, and models of myelinated axons were optimized for a combination of AP conduction velocity and energy efficiency.
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Propagation Speed in Myelinated Nerve: II. Theoretical Dependence on External Na+ and on Temperature

W.L. Hardy
- 01 Oct 1973 - 
TL;DR: The Hodgkin-Huxley (H.H.) equations modified by Dodge for Rana pipiens myelinated nerve have been solved to determine how well the theory predicts the effects of changes of temperature and [Na(+)](0) on propagation.
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Differences in potentials and excitability properties in simulated cases of demyelinating neuropathies. Part II. Paranodal demyelination.

TL;DR: The study shows that the excitability properties in demyelinating neuropathies are much more largely determined by the paranodal changes than by the internodalChanges, and provides new and important information about the pathophysiology of human Demyelinated Neuropathies.
Journal ArticleDOI

Sustained-release fampridine and the role of ion channel dysfunction in multiple sclerosis.

TL;DR: Clinical trials have demonstrated improvements in walking speed in patients receiving fampridine SR, a K+ channel blocker, which appears to be well-tolerated with a low risk of serious adverse events and provides benefits in both relapsing and progressive forms of MS.
Journal ArticleDOI

Propagation speed in myelinated nerve. I. Experimental dependence on external Na and on temperature.

W.L. Hardy
- 01 Oct 1973 - 
TL;DR: Conduction speed (theta) in single myelinated Rana pipiens sciatic nerve fibers has been precisely measured using intracellular recording and on-line digital computer techniques and theta has very close to a square root dependence on [Na(+)](0) for these fibers.
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