scholarly journals Assessment of 18F-PBR-111 in the Cuprizone Mouse Model of Multiple Sclerosis

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 786
Author(s):  
Valerie L. Jewells ◽  
Hong Yuan ◽  
Joseph R. Merrill ◽  
Jonathan E. Frank ◽  
Akhil Patel ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mouse Model ◽  
Animal Studies ◽  
Therapy Response ◽  
Internal Capsule ◽  
Structural Data ◽  
Brain Regions ◽  
Immunofluorescence Staining ◽  
In Vivo Evaluation

The study aims to assess site assessment of the performance of 18F-PBR-111 as a neuroinflammation marker in the cuprizone mouse model of multiple sclerosis (MS). 18F-PBR-111 PET imaging has not been well evaluated in multiple sclerosis applications both in preclinical and clinical research. This study will help establish the potential utility of 18F-PBR-111 PET in preclinical MS research and future animal and future human applications.18F-PBR-111 PET/CT was conducted at 3.5 weeks (n = 7) and 5.0 weeks (n = 7) after cuprizone treatment or sham control (n = 3) in the mouse model. A subgroup of mice underwent autoradiography with cryosectioned brain tissue. T2 weighted MRI was performed to obtain the brain structural data of each mouse. 18F-PBR-111 uptake was assessed in multiple brain regions with PET and autoradiography images. The correlation between autoradiography and immunofluorescence staining of neuroinflammation (F4/80 and CD11b) was measured. Compared to control mice, significant 18F-PBR-111 uptake in the corpus callosum (p < 0.001), striatum (caudate and internal capsule, p < 0.001), and hippocampus (p < 0.05) was identified with PET images at both 3.5 weeks and 5.0 weeks, and validated with autoradiography. No significant uptake differences were detected between 3.5 weeks and 5.0 weeks assessing these regions as a whole, although there was a trend of increased uptake at 5.0 weeks compared to 3.5 weeks in the CC. High 18F-PBR-111 uptake regions correlated with microglial/ macrophage locations by immunofluorescence staining with F4/80 and CD11b antibodies. 18F-PBR-111 uptake in anatomic locations correlated with activated microglia at histology in the cuprizone mouse model of MS suggests that 18F-PBR-111 has potential for in vivo evaluation of therapy response and potential for use in MS patients and animal studies.

scholarly journals Boosting postnatal oligodendrogenesis in a mouse model of Multiple Sclerosis

2020 ◽  
Author(s):  
Joana Mateus ◽  
Marta Alonso Gomes ◽  
Rita Félix Soares ◽  
Sara L. Paulo ◽  
Ângelo F. Chora ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mouse Model ◽  
Inflammatory Cytokine ◽  
Motor Impairment ◽  
Molecular Data ◽  
Brain Regions ◽  
Brain Parenchyma ◽  
Protein Levels

Under Multiple Sclerosis pathological conditions, oligodendrocyte precursor cells (OPCs) present in the brain parenchyma or derived from subventricular zone neural stem cells (SVZ-NSCs) can differentiate into oligodendrocytes (OLs), which migrate and partially remyelinate the lesioned areas. Previous data from our group demonstrated that activation of adenosine A2A receptors (A2AR) modulated SVZ-NSCs oligodendroglial differentiation, both in vitro and in vivo under physiological conditions. Hence, we aimed at understanding the role of A2AR in adult oligodendrogenesis derived from SVZ-NSCs in an in vivo mouse model of MS. For this, the Experimental Autoimmune Encephalomyelitis (EAE) mouse model of MS was developed, and behavioural tests were performed to evaluate motor function. Cellular differentiation was assessed by immunohistochemistry assays for bromodeoxyuridine (BrdU) colocalization with oligodendrocytic markers in brain regions of interest. Western blot and ELISA assays were used for myelin protein levels and inflammatory cytokine quantification. Our results for EAE model characterization showed that motor impairment is proportional to the score of the disease and cellular and molecular data showed an increase in the levels of the pro-inflammatory cytokine TNFα (n=5, p<0.01). A significant increase in NG2+BrdU+ cells in the corpus callosum (CC) of EAE mice was observed (n=3, p<0.05), hinting at the migration of OPCs from the SVZ to the CC. Ongoing studies encompass the in vivo modulation of A2AR and assessing its effect on EAE phenotype and adult oligodendrogenesis, ultimately unveiling the modulation of adult oligodendrogenesis derived from SVZ-NSCs by A2AR as a putative therapy for MS.

In Vivo Magnetic Resonance Imaging of Intravenously Injected Neural Stem Cells in a Mouse Model of Multiple Sclerosis

2006 ◽  
Vol 19 (5) ◽  
pp. 635-636
Author(s):  
L.S. Politi ◽  
S. Pluchino ◽  
M. Bacigaluppi ◽  
E. Brambilla ◽  
M. Cadioli ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Stem Cells ◽  
Magnetic Resonance ◽  
Mouse Model ◽  
Neural Stem Cells ◽  
Resonance Imaging

scholarly journals Gene expression in oligodendrocytes during remyelination reveals cholesterol homeostasis as a therapeutic target in multiple sclerosis

2019 ◽  
Vol 116 (20) ◽  
pp. 10130-10139 ◽  
Author(s):  
Rhonda R. Voskuhl ◽  
Noriko Itoh ◽  
Alessia Tassoni ◽  
Macy Akiyo Matsukawa ◽  
Emily Ren ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Corpus Callosum ◽  
Regional Differences ◽  
Cholesterol Synthesis ◽  
Brain Regions ◽  
Axonal Damage ◽  
Cholesterol Homeostasis ◽  
Sequencing Analysis

Regional differences in neurons, astrocytes, oligodendrocytes, and microglia exist in the brain during health, and regional differences in the transcriptome may occur for each cell type during neurodegeneration. Multiple sclerosis (MS) is multifocal, and regional differences in the astrocyte transcriptome occur in experimental autoimmune encephalomyelitis (EAE), an MS model. MS and EAE are characterized by inflammation, demyelination, and axonal damage, with minimal remyelination. Here, RNA-sequencing analysis of MS tissues from six brain regions suggested a focus on oligodendrocyte lineage cells (OLCs) in corpus callosum. Olig1-RiboTag mice were used to determine the translatome of OLCs in vivo in corpus callosum during the remyelination phase of a chronic cuprizone model with axonal damage. Cholesterol-synthesis gene pathways dominated as the top up-regulated pathways in OLCs during remyelination. In EAE, remyelination was induced with estrogen receptor-β (ERβ) ligand treatment, and up-regulation of cholesterol-synthesis gene expression was again observed in OLCs. ERβ-ligand treatment in the cuprizone model further increased cholesterol synthesis gene expression and enhanced remyelination. Conditional KOs of ERβ in OLCs demonstrated that increased cholesterol-synthesis gene expression in OLCs was mediated by direct effects in both models. To address this direct effect, ChIP assays showed binding of ERβ to the putative estrogen-response element of a key cholesterol-synthesis gene (Fdps). As fetal OLCs are exposed in utero to high levels of estrogens in maternal blood, we discuss how remyelinating properties of estrogen treatment in adults during injury may recapitulate normal developmental myelination through targeting cholesterol homeostasis in OLCs.

Enhanced in vivo efficacy of a long-life type I Interferon superagonist in a mouse model of multiple sclerosis

2014 ◽  
Vol 275 (1-2) ◽  
pp. 219
Author(s):  
Daniel Harari ◽  
Nadine Kallweit ◽  
Renne Abramovich ◽  
Keren Sasson ◽  
Alla Zozulya ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mouse Model ◽  
Type I Interferon ◽  
Type I ◽  
In Vivo Efficacy ◽  
Long Life ◽  
Life Type

In vivo evaluation of piperine and synthetic analogues as potential treatments for vitiligo using a sparsely pigmented mouse model

2008 ◽  
Vol 158 (5) ◽  
pp. 941-950 ◽  
Author(s):  
L. Faas ◽  
R. Venkatasamy ◽  
R.C. Hider ◽  
A.R. Young ◽  
A. Soumyanath
Keyword(s):  
Mouse Model ◽  
Synthetic Analogues ◽  
In Vivo Evaluation

A new simple mouse model for the in vivo evaluation of cholecystokinin (CCK) antagonists: Comparative potencies and durations of action of nonpeptide antagonists

Life Sciences ◽  
1986 ◽  
Vol 39 (18) ◽  
pp. 1631-1638 ◽  
Author(s):  
Victor J. Lotti ◽  
Deborah J. Cerino ◽  
Paul J. Kling ◽  
Raymond S.L. Chang
Keyword(s):  
Mouse Model ◽  
In Vivo Evaluation ◽  
Cck Antagonists

scholarly journals Modulated focused ultrasound for treatment of de-myelinating axons in multiple sclerosis lesions – pilot animal studies

2018 ◽  
Author(s):  
Pierre D. Mourad
Keyword(s):  
Multiple Sclerosis ◽  
Mouse Model ◽  
Brain Tissue ◽  
Neurological Disorders ◽  
Animal Studies ◽  
Focused Ultrasound ◽  
Neural Circuits ◽  
Laser Light ◽  
Non Invasive ◽  
Pulsed Focused Ultrasound

Multiple sclerosis is a debilitating disease whose symptoms arise from de-myelination of axons within brain tissue with an attendant loss of central and peripheral function. We among others have shown that transcranial delivery of pulsed focused ultrasound (pFU) can non-destructively activate central neural circuits. Others have shown enhanced myelin remodeling of axons activated by laser light in an optogenetic mouse model. We hypothesize that pFU activation of axons within MS lesions in a rodent model will decrease their de-myelination and increase their re-myelination. If successful, this non-invasive therapy may lead to rapid advancements in the treatment of MS and other de-myelinating neurological disorders.

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