A new focal EAE model of cortical demyelination: Multiple sclerosis-like lesions with rapid resolution of inflammation and extensive remyelination
Abstract
Recent studies have revealed widespread demyelination in the cortex of patients with chronic multiple sclerosis. In contrast to white matter lesions, cortical multiple sclerosis lesions are accompanied by only minor inflammation. Research into the pathogenesis of cortical lesion formation has been hampered by the fact that the conventional rodent model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), does not regularly affect the cortex. To overcome this limitation we developed a new rat model of cortical multiple sclerosis. Lesions were stereotactically targeted to the cerebral cortex by injection of pro-inflammatory mediators in animals that were immunized subclinically with myelin oligodendrocyte glycoprotein (MOG). We thus generated highly reproducible demyelinated lesions in the neocortex with remarkable histological similarities to cortical multiple sclerosis lesions. The focal cortical EAE model led to the typical pattern of intracortical and subpial demyelination, infiltration with inflammatory cells, complement deposition, acute axonal damage and neuronal cell death. Surprisingly, extensive cortical inflammation largely resolved within 2 weeks. Furthermore, cortical demyelination was readily compensated by rapid remyelination. Our data thus suggest that cortical inflammation is a transient phenomenon, and that remyelination of cortical inflammatory-demyelinating lesions may occur rapidly.
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The efficacy of remyelination depends on multiple factors such as age, disease duration and lesion location.
“The efficacy of remyelination has been shown to depend on multiple factors such as, age, disease duration and lesion location.”
From BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis (2025) · cites this paper as [9]
Cites
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“Furthermore, apoptotic neurons and transected neurites were described in cortical lesions of patients (Peterson et al., 2001).”
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Remyelination in the CNS: from biology to therapy
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Regenerating CNS myelin — from mechanisms to experimental medicines
Franklin, R. J. M., & ffrench-Constant, C. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.136 · Cited by 647 · see citing works
Alzheimer's disease as homeostatic responses to age-related myelin breakdown
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BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis
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Self-citationFrom insights to innovations: evaluating preclinical paradigms in demyelinating disease therapeutics
Karbalaee, M., Lin, A., Peruzzotti-Jametti, L., Pluchino, S., & Mozafari, S. (2026) · Lab Animal · doi:10.1038/s41684-026-01725-6 · Cited by 2 · see citing works
“…with myelin peptides (for example, MOG 1–125 or MOG 35–55 ), produces localized inflammatory demyelinating lesions that enable precise spatial and temporal analysis of lesion evolution; however, the model may lack overt EAE behavioral phenotypes depending on the CNS region targeted 121–123 .”
- Authors
- Merkler, D.
- Affiliations
- University of Göttingen (DE)
- Corresponding author
- Merkler, D.
- ORCID
- Merkler, D.
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-07-01
- Volume
- 129
- Issue
- 8
- Pages
- 1972-1983
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2155221060
- Cited by
- 222
- References
- 2
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 10 · 2022: 6 · 2021: 14 · 2020: 7 · 2019: 13 · 2018: 13 · 2017: 19 · 2016: 8 · 2015: 12 · 2014: 8 · 2013: 20 · 2012: 14
- FWCI
- 10.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- GRO (submittedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Keywords
- cortical demyelination, multiple sclerosis, experimental autoimmune encephalomyelitis, rat model, myelin oligodendrocyte glycoprotein, stereotactic injection, remyelination, cortical inflammation, complement deposition, axonal injury, neuronal cell death
- MeSH terms
- Animals, Cerebral Cortex, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Female, Multiple Sclerosis, Myelin Proteins, Myelin Sheath, Rats, Inbred Lew, Remission, Spontaneous, Stereotaxic Techniques, Cytokines, Inflammation Mediators, Myelin-Associated Glycoprotein, Rats, Myelin-Oligodendrocyte Glycoprotein
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