Demyelination and remyelination detected in an alternative cuprizone mouse model of multiple sclerosis with 7.0 T multiparameter magnetic resonance imaging

Abstract

The aim of this study was to investigate the mechanisms underlying demyelination and remyelination with 7.0 T multiparameter magnetic resonance imaging (MRI) in an alternative cuprizone (CPZ) mouse model of multiple sclerosis (MS). Sixty mice were divided into six groups (n = 10, each), and these groups were imaged with 7.0 T multiparameter MRI and treated with an alternative CPZ administration schedule. T2-weighted imaging (T2WI), susceptibility-weighted imaging (SWI), and diffusion tensor imaging (DTI) were used to compare the splenium of the corpus callosum (sCC) among the groups. Prussian blue and Luxol fast blue staining were performed to assess pathology. The correlations of the mean grayscale value (mGSV) of the pathology results and the MRI metrics were analyzed to evaluate the multiparameter MRI results. One-way ANOVA and post hoc comparison showed that the normalized T2WI (T2-nor), fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) values were significantly different among the six groups, while the mean phase (Φ) value of SWI was not significantly different among the groups. Correlation analysis showed that the correlation between the T2-nor and mGSV was higher than that among the other values. The correlations among the FA, RD, MD, and mGSV remained instructive. In conclusion, ultrahigh-field multiparameter MRI can reflect the pathological changes associated with and the underlying mechanisms of demyelination and remyelination in MS after the successful establishment of an acute CPZ-induced model.

Motor Behavioral Deficits in the Cuprizone Model: Validity of the Rotarod Test Paradigm

“…In most cases, histological and ultrastructural readouts are performed to evaluate the effectiveness of novel treatment strategies. Luxol-fast blue stains and immunohistochemistry using antibodies directed against major myelin proteins such as anti-proteolipid protein (PLP) or anti-myelin basic protein (MBP), for example, are frequently applied to estimate the myelination levels of the region of interest [ 36 , 37 , 38 ]. Ultrastructural studies using electron microscopy can verify the histological results and analyze the axonal myelin diameter ratio, also called “G-ratio”, which is believed to be a sensitive marker for remyelinated axons [ 39 ].…”

Replenishing the Aged Brains: Targeting Oligodendrocytes and Myelination?

“…Advances in neuroimaging contributes to explore macroscopical and microstructural changes in white matter ( Ding et al, 2021 ; Kolb et al, 2021 ). Taking advantage of MRI imaging and diffusion tensor imaging (DTI), a variety of age-related white matter changes, including reduced white matter volume, white matter lesions, disrupted white matter integrity, and subsequent cortical disconnection have all been observed in normal aging brains ( Caligiuri et al, 2015 ).…”

Performance in information processing speed is associated with parietal white matter tract integrity in multiple sclerosis

“…Here, we investigated structural white matter alterations in MS patients to better understand the role of specific parietal white matter tracts, especially the SLF, and their associations with ability on the SDMT. We focused on tract integrity as quantified by fractional anisotropy (FA) using diffusion tractography (DTI) on diffusion weighted imaging (DWI), as FA is a highly sensitive, early, diffusion tensor-derived metric for demyelination (21). In the literature, different DTI methods are used -either in a whole brain approach, called tract based spatial statistics (6), or with a more hypothesis driven, regional approach.…”