Related Experiment Video
Updated: Aug 7, 2026
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Differential macrophage/microglia activation in neocortical EAE lesions in the marmoset monkey
Doron Merkler1, Robert Böscke, Barthel Schmelting
1Department of Neuropathology, Georg-August University Göttingen, Göttingen, Germany. merkler@med.uni-goettingen.de
Abstract:
Recent studies revealed an important involvement of the cerebral cortex in multiple sclerosis (MS) patients. Cortical lesions in MS were reported to be less inflammatory and to show less structural damage than white matter lesions. Animal models reflecting the histopathological hallmarks of cortical demyelinated lesions in MS are sparse. Induction of experimental autoimmune encephalomyelitis (EAE) in the common marmoset has turned out to be an attractive non-human-primate model for MS. In the present study we investigated the presence and detailed cellular composition of cortical inflammatory demyelinating pathology in the common marmoset upon immunization with myelin oligodendrocyte glycoprotein (MOG). Extensive cortical demyelination reflecting the topographically distinct cortical lesion types in MS patients was revealed by immunohistochemistry for myelin basic protein (MBP). We explored the density of T- and B-lymphocytes, MHC-II expressing macrophages/microglia cells and early activated macrophages (MRP14) at perivascular and parenchymal lesions sites in neocortex and subcortical white matter. Despite a similar density of perivascular inflammatory infiltrates in the demyelinated neocortex, a considerable lower fraction of macrophages was found to express MRP14 in the neocortex indicating a different activation pattern in cortical compared with white matter lesions. Furthermore, cortical EAE lesions in marmoset monkeys revealed immunoglobulin leakage and complement component C9 deposition in intracortical but not subpial demyelination. Our findings indicate that the inflammatory response, especially macrophage and microglia activation, may be regulated differently in gray matter areas in primate brain.
Insights
This study reveals distinct inflammatory responses in the cerebral cortex of marmoset models of multiple sclerosis (MS). Macrophage activation patterns differ between cortical and white matter lesions, suggesting unique gray matter immune regulation in primates.
Area of Science:
- Neuroimmunology
- Demyelinating Diseases
- Primate Models
Background:
- Cerebral cortex involvement in multiple sclerosis (MS) is increasingly recognized.
- Cortical MS lesions exhibit distinct inflammatory and damage profiles compared to white matter lesions.
- Existing animal models inadequately replicate cortical demyelination seen in MS.
Purpose of the Study:
- To investigate cortical inflammatory demyelinating pathology in a common marmoset model of experimental autoimmune encephalomyelitis (EAE).
- To characterize the cellular composition of these cortical lesions.
- To compare inflammatory patterns in cortical versus white matter lesions.
Main Methods:
- Induction of EAE in common marmosets using myelin oligodendrocyte glycoprotein (MOG).
- Immunohistochemistry for myelin basic protein (MBP), T- and B-lymphocytes, MHC-II, and MRP14.
- Analysis of perivascular and parenchymal lesions in neocortex and white matter.
Main Results:
- Extensive cortical demyelination was observed, mirroring MS lesion types.
- Macrophage activation (MRP14 expression) was lower in neocortical lesions compared to white matter lesions.
- Immunoglobulin leakage and complement C9 deposition occurred in intracortical, but not subpial, demyelination.
Conclusions:
- The common marmoset EAE model displays relevant cortical demyelination.
- Macrophage and microglia activation patterns differ between gray and white matter lesions in the primate brain.
- These findings suggest distinct immune regulation in gray matter during primate neuroinflammation.
