scholarly journals Melatonin Therapy Modulates Cerebral Metabolism and Enhances Remyelination by Increasing PDK4 in a Mouse Model of Multiple Sclerosis

2019 ◽  
Vol 10 ◽  
Author(s):  
Majid Ghareghani ◽  
Linda Scavo ◽  
Yahya Jand ◽  
Naser Farhadi ◽  
Hossein Sadeghi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mouse Model ◽  
Cerebral Metabolism

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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shuang Ding ◽  
Yu Guo ◽  
Xiaoya Chen ◽  
Silin Du ◽  
Yongliang Han ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Mouse Model ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Blue Staining ◽  
Resonance Imaging ◽  
The Mean ◽  
Underlying Mechanisms

AbstractThe 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.

scholarly journals Astrocyte Glutamate Uptake and Water Homeostasis Are Dysregulated in the Hippocampus of Multiple Sclerosis Patients With Seizures

ASN NEURO ◽  
2020 ◽  
Vol 12 ◽  
pp. 175909142097960
Author(s):  
Andrew S. Lapato ◽  
Sarah M. Thompson ◽  
Karen Parra ◽  
Seema K. Tiwari-Woodruff
Keyword(s):  
Multiple Sclerosis ◽  
Mouse Model ◽  
Regional Differences ◽  
Neuronal Excitability ◽  
Demyelinating Disease ◽  
Glutamate Uptake ◽  
Cx43 Expression ◽  
Water Homeostasis ◽  
Hippocampal Astrocytes ◽  
Multiple Sclerosis Patients

While seizure disorders are more prevalent among multiple sclerosis (MS) patients than the population overall and prognosticate earlier death & disability, their etiology remains unclear. Translational data indicate perturbed expression of astrocytic molecules contributing to homeostatic neuronal excitability, including water channels (AQP4) and synaptic glutamate transporters (EAAT2), in a mouse model of MS with seizures (MS+S). However, astrocytes in MS+S have not been examined. To assess the translational relevance of astrocyte dysfunction observed in a mouse model of MS+S, demyelinated lesion burden, astrogliosis, and astrocytic biomarkers (AQP4/EAAT2/ connexin-CX43) were evaluated by immunohistochemistry in postmortem hippocampi from MS & MS+S donors. Lesion burden was comparable in MS & MS+S cohorts, but astrogliosis was elevated in MS+S CA1 with a concomitant decrease in EAAT2 signal intensity. AQP4 signal declined in MS+S CA1 & CA3 with a loss of perivascular AQP4 in CA1. CX43 expression was increased in CA3. Together, these data suggest that hippocampal astrocytes from MS+S patients display regional differences in expression of molecules associated with glutamate buffering and water homeostasis that could exacerbate neuronal hyperexcitability. Importantly, mislocalization of CA1 perivascular AQP4 seen in MS+S is analogous to epileptic hippocampi without a history of MS, suggesting convergent pathophysiology. Furthermore, as neuropathology was concentrated in MS+S CA1, future study is warranted to determine the pathophysiology driving regional differences in glial function in the context of seizures during demyelinating disease.

scholarly journals Bowman–Birk inhibitor suppresses autoimmune inflammation and neuronal loss in a mouse model of multiple sclerosis

2008 ◽  
Vol 271 (1-2) ◽  
pp. 191-202 ◽  
Author(s):  
Tarik Touil ◽  
Bogoljub Ciric ◽  
Elvira Ventura ◽  
Kenneth S. Shindler ◽  
Bruno Gran ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mouse Model ◽  
Neuronal Loss ◽  
Autoimmune Inflammation

scholarly journals Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e79188 ◽  
Author(s):  
Katie Lidster ◽  
Samuel J. Jackson ◽  
Zubair Ahmed ◽  
Peter Munro ◽  
Pete Coffey ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mouse Model

scholarly journals The translocator protein ligand XBD173 improves clinical symptoms and neuropathological markers in the SJL/J mouse model of multiple sclerosis

2017 ◽  
Vol 1863 (12) ◽  
pp. 3016-3027 ◽  
Author(s):  
Géraldine Leva ◽  
Christian Klein ◽  
Jérémie Benyounes ◽  
François Hallé ◽  
Frédéric Bihel ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mouse Model ◽  
Clinical Symptoms ◽  
Translocator Protein

scholarly journals A higher proportion of ermin-immunopositive oligodendrocytes in areas of remyelination

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256155
Author(s):  
Intakhar Ahmad ◽  
Stig Wergeland ◽  
Eystein Oveland ◽  
Lars Bø
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Corpus Callosum ◽  
Mouse Model ◽  
Grey Matter ◽  
Early Stage ◽  
Relative Proportion ◽  
Normal Appearing White Matter ◽  
The Brain

Incomplete remyelination is frequent in multiple sclerosis (MS)-lesions, but there is no established marker for recent remyelination. We investigated the role of the oligodendrocyte/myelin protein ermin in de- and remyelination in the cuprizone (CPZ) mouse model, and in MS. The density of ermin+ oligodendrocytes in the brain was significantly decreased after one week of CPZ exposure (p < 0.02). The relative proportion of ermin+ cells compared to cells positive for the late-stage oligodendrocyte marker Nogo-A increased at the onset of remyelination in the corpus callosum (p < 0.02). The density of ermin-positive cells increased in the corpus callosum during the CPZ-phase of extensive remyelination (p < 0.0001). In MS, the density of ermin+ cells was higher in remyelinated lesion areas compared to non-remyelinated areas both in white- (p < 0.0001) and grey matter (p < 0.0001) and compared to normal-appearing white matter (p < 0.001). Ermin immunopositive cells in MS-lesions were not immunopositive for the early-stage oligodendrocyte markers O4 and O1, but a subpopulation was immunopositive for Nogo-A. The data suggest a relatively higher proportion of ermin immunopositivity in oligodendrocytes compared to Nogo-A indicates recent or ongoing remyelination.

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