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Combination of cuprizone and experimental autoimmune encephalomyelitis to study inflammatory brain lesion formation and progression.
- Source :
-
Glia [Glia] 2017 Dec; Vol. 65 (12), pp. 1900-1913. Date of Electronic Publication: 2017 Aug 24. - Publication Year :
- 2017
-
Abstract
- Brain-intrinsic degenerative cascades are a proposed factor driving inflammatory lesion formation in multiple sclerosis (MS) patients. We recently described a model combining noninflammatory cytodegeneration (via cuprizone) with the classic active experimental autoimmune encephalomyelitis (Cup/EAE model), which exhibits inflammatory forebrain lesions. Here, we describe the histopathological characteristics and progression of these Cup/EAE lesions. We show that inflammatory lesions develop at various topographical sites in the forebrain, including white matter tracts and cortical and subcortical grey matter areas. The lesions are characterized by focal demyelination, discontinuation of the perivascular glia limitans, focal axonal damage, and neutrophil granulocyte extravasation. Transgenic mice with enhanced green fluorescent protein-expressing microglia and red fluorescent protein-expressing monocytes reveal that both myeloid cell populations contribute to forebrain inflammatory infiltrates. EAE-triggered inflammatory cerebellar lesions were augmented in mice pre-intoxicated with cuprizone. Gene expression studies suggest roles of the chemokines Cxcl10, Ccl2, and Ccl3 in inflammatory lesion formation. Finally, follow-up experiments in Cup/EAE mice with chronic disease revealed that forebrain, but not spinal cord, lesions undergo spontaneous reorganization and repair. This study underpins the significance of brain-intrinsic degenerative cascades for immune cell recruitment and, in consequence, MS lesion formation.<br /> (© 2017 Wiley Periodicals, Inc.)
- Subjects :
- Amyloid beta-Protein Precursor metabolism
Animals
Disease Models, Animal
Encephalitis genetics
Encephalomyelitis, Autoimmune, Experimental immunology
Female
Freund's Adjuvant toxicity
Gene Expression drug effects
Gene Expression genetics
Glial Fibrillary Acidic Protein metabolism
Intercellular Adhesion Molecule-1 genetics
Intercellular Adhesion Molecule-1 metabolism
Luminescent Proteins genetics
Luminescent Proteins metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microglia pathology
Microglia ultrastructure
Monocytes pathology
Monocytes ultrastructure
Myelin-Oligodendrocyte Glycoprotein immunology
Myelin-Oligodendrocyte Glycoprotein toxicity
Peptide Fragments immunology
Peptide Fragments toxicity
Receptors, CCR2 genetics
Receptors, CCR2 metabolism
Receptors, Interleukin-8A genetics
Receptors, Interleukin-8A metabolism
Disease Progression
Encephalitis etiology
Encephalitis pathology
Encephalomyelitis, Autoimmune, Experimental complications
Sesquiterpenes toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1098-1136
- Volume :
- 65
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Glia
- Publication Type :
- Academic Journal
- Accession number :
- 28836302
- Full Text :
- https://doi.org/10.1002/glia.23202