Microglia-derived CCL2 has a prime role in neocortex neuroinflammation

Area of Science:

• Neuroscience
• Immunology
• Stem Cell Biology

Background:

• Experimental autoimmune encephalomyelitis (EAE) in mice shows demyelination and blood-brain barrier (BBB) impairment in the cerebral cortex.
• Mesenchymal stem cells (MSCs) are known to control neuroinflammation and astrogliosis in EAE.
• Understanding the cellular sources of CCL2 is crucial for EAE pathogenesis and MSC therapeutic mechanisms.

Purpose of the Study:

• To investigate the cellular source of chemokine CCL2 in the neocortex of EAE-affected mice.
• To analyze the effect of mesenchymal stem cell (MSC) treatment on CCL2 expression and neuroinflammation in EAE.
• To elucidate the role of microglia and CCL2 in EAE pathogenesis and MSC therapeutic effects.

Main Methods:

• Immunohistochemistry (IHC) and dual RNAscope IHC/in situ hybridization were employed.
• Specific markers for astrocytes, NG2-glia, macrophages, and microglia were used in conjunction with CCL2.
• Analysis focused on the cellular localization of CCL2 in the neocortex of EAE mice with and without MSC treatment.

Main Results:

• Hypertrophic microglia were identified as the primary source of CCL2 in EAE-affected mouse neocortex.
• CCL2-producing microglia surrounded cortical neurons and damaged BBB microvessels.
• MSC treatment rapidly and persistently reduced microgliosis and CCL2 expression, preserving BBB integrity.

Conclusions:

• Microgliosis with high CCL2 expression is a key feature of EAE in the mouse neocortex.
• MSC treatment effectively controls neuroinflammation and BBB permeability in EAE.
• These findings have significant implications for understanding EAE pathogenesis and developing MSC-based therapies for related human diseases.