Abstract

Event Abstract Back to Event In-Vivo Mouse Brain DT-MRI: Assessment of Gender Specific Response to the Thyroid Hormone Remyelinating Treatment Laura-Adela Harsan1*, Alexandru Parlog1, Neele Hübner1, Jürgen Hennig1 and Dominik Von Elverfeldt1 1 University Hospital Center, Freiburg, Department of Radiology, Germany Multiple Sclerosis (MS) is one of the most common neurological disorders, characterized by extensive loss of myelin, axonal damage and inflammation of the central nervous system axonal tracts. It affects twice more women than men and its progression is gender dependent; the male patients having a faster and more severe outcome. Therefore, the response to different therapeutic strategies might be gender specific. Various features of the MS are mimicked in animal models. Long-term 0.2% cuprizone feeding in mice produces severe brain demyelination, accompanied by gliosis, astrocytic hypertrophy and axonal injury (1), with a stronger demyelination outcome in male animals (2). Noninvasive in vivo diffusion tensor magnetic resonance imaging (DT-MRI) was used here to comparatively quantify, in a longitudinal study, the demyelination extent and the efficacy of a thyroid hormone (T3, tri-idothyronine) based therapy for inducing recovery in demyelinated male and female mouse brains. The mice were imaged using a 9.4T small bore animal Scanner (Biospec 94/20, Bruker) and a 4-shots DTI-EPI sequence. The brain pathologic alterations induced by cuprizone caused changes of DT-MRI derived parameter values, including loss of white matter anisotropy and increase of water diffusion values perpendicular to the fiber tracts (D_radial). These pathological features were maintained in both male and females animals which were not subjected to hormonal therapy. The mice receiving thyroid hormone for 3 weeks showed progressive recovery towards normal radial diffusivity values during the 12 weeks of observation. Both males and female mice positively responded to the remyelinating therapy. A certain trend of faster and more consistent recovery was observed in the female mice, which shown decrease of the radial diffusivity immediately after T3 treatment. Similar features of faster remyelination and oligodendrogenesis were observed in the histopathological investigation. This might suggest greater myelinating potential of the newly formed female oligodendrocytes or greater sensitivity to the T3 actions. The results are valuable for understanding the role of gender in the physiopathology and the remyelination of the white matter. In the view of future translation of the preclinical assays in the clinical environment, DT-MRI investigation is of high value, allowing the quantitative survey of the same individuals overtime. Acknowledgements This work was supported by a Humboldt Foundation Grant to LH References 1: Matsushima and Morell 2001, 2: Harsan et al., ISMRM 2010 Keywords: cuprizone mouse model, DT-MRI, remyelination, Thyroid hormone Conference: BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011, Freiburg, Germany, 4 Oct - 6 Oct, 2011. Presentation Type: Poster Topic: brain disease, network dysfunction and intervention (please use "brain disease, network dysfunction and intervention" as keyword) Citation: Harsan L, Parlog A, Hübner N, Hennig J and Von Elverfeldt D (2011). In-Vivo Mouse Brain DT-MRI: Assessment of Gender Specific Response to the Thyroid Hormone Remyelinating Treatment. Front. Comput. Neurosci. Conference Abstract: BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011. doi: 10.3389/conf.fncom.2011.53.00191 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Aug 2011; Published Online: 04 Oct 2011. * Correspondence: Dr. Laura-Adela Harsan, University Hospital Center, Freiburg, Department of Radiology, Freiburg, Germany, laura.harsan@uniklinik-freiburg.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Laura-Adela Harsan Alexandru Parlog Neele Hübner Jürgen Hennig Dominik Von Elverfeldt Google Laura-Adela Harsan Alexandru Parlog Neele Hübner Jürgen Hennig Dominik Von Elverfeldt Google Scholar Laura-Adela Harsan Alexandru Parlog Neele Hübner Jürgen Hennig Dominik Von Elverfeldt PubMed Laura-Adela Harsan Alexandru Parlog Neele Hübner Jürgen Hennig Dominik Von Elverfeldt Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Highlights

  • Multiple Sclerosis (MS) is one of the most common neurological disorders, characterized by extensive loss of myelin, axonal damage and inflammation of the central nervous system (CNS) axonal tracts (1)

  • We recently evidenced by DT-MRI of the cuprizone demyelinated mouse brains; gender related differences in the development of the white matter pathology (3), with more severe axonal damage in the male animals

  • Similar features of faster myelin recovery were observed in the histopathological investigation, a strong effect of induced ologodendrogenesis in both genders was quantified at already week w12+3 (Fig.2-b-C,F)

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Summary

Introduction

Multiple Sclerosis (MS) is one of the most common neurological disorders, characterized by extensive loss of myelin, axonal damage and inflammation of the central nervous system (CNS) axonal tracts (1) It affects twice more women than men and the progression is gender dependent; the male patients having a faster and more severe outcome. The main goal of the present study was to comparatively investigate the response of the cuprizone demyelinated male and female mice to a remyelinating therapy based on thyroid hormones (T3, tri-idothyronine). This therapy was very efficient in one of our previous studies (4) for inducing remyelination in female mice, but no longitudinal investigation was performed in male animals so far

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