Dynamic response of microglia/macrophage polarization following demyelination in mice

• Published in: Journal of neuroinflammation Vol. 16; no. 1; pp. 188 - 22
• Main Authors: Chu, Tianci, Zhang, Yi Ping, Tian, Zhisen, Ye, Chuyuan, Zhu, Mingming, Shields, Lisa B E, Kong, Maiying, Barnes, Gregory N, Shields, Christopher B, Cai, Jun
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 17-10-2019; BioMed Central; BMC
• Subjects: Animals; Antigen presentation; Astrocytes; Brain research; Cell activation; Cell differentiation; Cytokines; Demyelinating Diseases - diagnostic imaging; Demyelinating Diseases - metabolism; Demyelination; Female; Focal demyelination model; Genetic aspects; Glial stem cells; Hand Strength - physiology; Inflammation; Lesions; Lipopolysaccharides; Macrophages; Macrophages - metabolism; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Medical examination; Mice; Mice, Inbred C57BL; Microglia; Microglia - metabolism; Microglia/macrophage; Multiple sclerosis; Myelination; Neuroinflammation; Neuronal-glial interactions; Observations; Oligodendrocyte/oligodendrocyte progenitor cells; Oligodendrocytes; Phenotypes; Plaques; Polarization; Progenitor cells; Sensorimotor function; Sensorimotor system; Surgery; Temporal variations; United States; Sensorimotor function; Multiple sclerosis; Neuroinflammation; Microglia/macrophage; Oligodendrocyte/oligodendrocyte progenitor cells; Focal demyelination model; Diffusion tensor imaging
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/s12974-019-1586-1

The glial response in multiple sclerosis (MS), especially for recruitment and differentiation of oligodendrocyte progenitor cells (OPCs), predicts the success of remyelination of MS plaques and return of function. As a central player in neuroinflammation, activation and polarization of microglia/macrophages (M/M) that modulate the inflammatory niche and cytokine components in demyelination lesions may impact the OPC response and progression of demyelination and remyelination. However, the dynamic behaviors of M/M and OPCs during demyelination and spontaneous remyelination are poorly understood, and the complex role of neuroinflammation in the demyelination-remyelination process is not well known. In this study, we utilized two focal demyelination models with different dynamic patterns of M/M to investigate the correlation between M/M polarization and the demyelination-remyelination process.
The temporal and spatial features of M/M activation/polarization and OPC response in two focal demyelination models induced by lysolecithin (LPC) and lipopolysaccharide (LPS) were examined in mice. Detailed discrimination of morphology, sensorimotor function, diffusion tensor imaging (DTI), inflammation-relevant cytokines, and glial responses between these two models were analyzed at different phases.
The results show that LPC and LPS induced distinctive temporal and spatial lesion patterns. LPS produced diffuse demyelination lesions, with a delayed peak of demyelination and functional decline compared to LPC. Oligodendrocytes, astrocytes, and M/M were scattered throughout the LPS-induced demyelination lesions but were distributed in a layer-like pattern throughout the LPC-induced lesion. The specific M/M polarization was tightly correlated to the lesion pattern associated with balance beam function.
This study elaborated on the spatial and temporal features of neuroinflammation mediators and glial response during the demyelination-remyelination processes in two focal demyelination models. Specific M/M polarization is highly correlated to the demyelination-remyelination process probably via modulations of the inflammatory niche, cytokine components, and OPC response. These findings not only provide a basis for understanding the complex and dynamic glial phenotypes and behaviors but also reveal potential targets to promote/inhibit certain M/M phenotypes at the appropriate time for efficient remyelination.