Dataset Information

The spectrum of spinal cord lesions in a primate model of multiple sclerosis.

ABSTRACT:

Background

Experimental autoimmune encephalomyelitis (EAE) in the common marmoset is a nonhuman primate model of multiple sclerosis (MS) that shares numerous clinical, radiological, and pathological features with MS. Among the clinical features are motor and sensory deficits that are highly suggestive of spinal cord (SC) damage.

Objective

To characterize the extent and nature of SC damage in symptomatic marmosets with EAE using a combined magnetic resonance imaging (MRI) and histopathology approach.

Materials and methods

SC tissues from five animals were scanned using 7 T MRI to collect high-resolution ex vivo images. Lesions were segmented and classified based on shape, size, and distribution along the SC. Tissues were processed for histopathological characterization (myelin and microglia/macrophages). Statistical analysis, using linear mixed-effects models, evaluated the association between MRI and histopathology.

Results

Marmosets with EAE displayed two types of SC lesions: focal and subpial lesions. Both lesion types were heterogeneous in size and configuration and corresponded to areas of marked demyelination with high density of inflammatory cells. Inside the lesions, the MRI signal was significantly correlated with myelin content (p < 0.001).

Conclusions

Our findings underscore the relevance of this nonhuman primate EAE model for better understanding mechanisms of MS lesion formation in the SC.

SUBMITTER: Lefeuvre JA

PROVIDER: S-EPMC6685769 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

The spectrum of spinal cord lesions in a primate model of multiple sclerosis.

Lefeuvre Jennifer A JA Guy Joseph R JR Luciano Nicholas J NJ Ha Seung-Kwon SK Leibovitch Emily E Santin Mathieu D MD Silva Afonso C AC Jacobson Steven S Lehéricy Stéphane S Reich Daniel S DS Sati Pascal P

Multiple sclerosis (Houndmills, Basingstoke, England) 20190207 3

<h4>Background</h4>Experimental autoimmune encephalomyelitis (EAE) in the common marmoset is a nonhuman primate model of multiple sclerosis (MS) that shares numerous clinical, radiological, and pathological features with MS. Among the clinical features are motor and sensory deficits that are highly suggestive of spinal cord (SC) damage.<h4>Objective</h4>To characterize the extent and nature of SC damage in symptomatic marmosets with EAE using a combined magnetic resonance imaging (MRI) and histo ...[more]

PMID: 30730246

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Project description:Infiltration of macrophages into the central nervous system and activation of microglia are hallmarks of multiple sclerosis and its animal model-experimental autoimmune encephalomyelitis (EAE). Cell death in EAE has been demonstrated as an essential mechanism in the local regulation of the inflammatory reaction, but also as one of the major factors contributing to the destruction of the nervous tissue. The focus of this study was on detection of cell death among ED1(+) cells (macrophages/activated microglia) in the spinal cord of Dark Agouti rats at the peak of EAE. Cell death was assessed using the TUNEL assay and immunostaining for cleaved caspase 3, as markers for cell death in general and "classical" apoptosis, respectively. Major infiltrates of immune cells were detected both in white matter and gray matter of spinal cords in rats at the disease peak. ED1, TUNEL, and caspase 3 positive cells were detected within, but also outside the infiltrates. There were more dying ED1(+) cells in white matter than in gray matter, both in the general population and in infiltrated regions. The observed discrepancy in the proportion of dying ED1(+) cells in spinal cord gray and white matter indicated that in EAE rat macrophages/microglia within gray matter are less prone to cell death induction. This is of special interest in the context of the increasingly appreciated contribution of spinal cord gray matter inflammation to multiple sclerosis pathogenesis. Our findings suggest that activated macrophages/microglia of gray matter are less susceptible to cell death induction. Alternatively, it can be assumed that intrinsic cell death-inductive mechanisms of nervous tissue differ in white and gray matter. Thus, further research on the gray matter macrophages/microglia cell death during EAE is warranted. They should be aimed at identification of the reasons for the observed differences and finding suitable ways to stimulate gray matter activated macrophages/microglia death.

Dataset Information

The spectrum of spinal cord lesions in a primate model of multiple sclerosis.

Background

Objective

Materials and methods

Results

Conclusions

Publications

The spectrum of spinal cord lesions in a primate model of multiple sclerosis.

Similar Datasets

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