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Updated: Jul 6, 2026
Identifying Microglia and Peripheral Infiltrating Macrophages in the Injured Spinal Cords Using Flow Cytometry
Published on: June 24, 2025
Spinal cord microglia exhibit a dysfunctional response to myelin damage
Matthew C Zupan1, Jack M Petersen1, Addison C Stover1
1Department of Chemistry, University of Kansas, 2030 Becker Dr, Lawrence, KS 66047, United States of America.
Abstract:
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that affects both the brain and spinal cord, although the brain has historically received greater attention. In the inducible, oligodendrocyte-specific knockout model of Myrf, which results in white matter damage to both the brain and spinal cord, our laboratory previously demonstrated that the brain undergoes remyelination following white matter damage, whereas the spinal cord has limited remyelination. We also observed that brain microglia display a much stronger activation than spinal cord microglia. Microglia regulate remyelination by clearing myelin debris, processing resulting lipids, and modulating the inflammation response. Therefore, we hypothesized that microglia are involved in limiting spinal cord remyelination in this model, either by having a limited phagocytosis response or by causing neuroinflammation. To test our hypothesis, we characterized microglial phenotypes during demyelination in both brain and spinal cord in the Myrf demyelination model. The brain exhibited an earlier microglial activation response and showed a higher percentage of microglia expressing phagocytic markers, suggesting a primed state for responding to damage. In contrast, spinal cord microglia showed a delayed increase in cells expressing phagocytic markers, sustained inflammation, and a predominately ameboid morphology during demyelination. Together, these findings in the Myrf demyelination model indicate that brain microglia mount a timely and coordinated response to demyelination that supports remyelination, whereas spinal cord microglia adopt a dysfunctional phenotype that likely contributes to reduced myelin repair.
Insights
Microglia in the brain promote remyelination after central nervous system damage. In contrast, spinal cord microglia show delayed responses and sustained inflammation, limiting myelin repair in multiple sclerosis models.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Multiple sclerosis (MS) is a central nervous system (CNS) demyelinating disease impacting brain and spinal cord.
- Brain exhibits more remyelination than spinal cord post-damage in the Myrf knockout model.
- Microglia play key roles in myelin debris clearance, lipid processing, and inflammation modulation during remyelination.
Purpose of the Study:
- To investigate the role of microglia in differential remyelination observed between the brain and spinal cord in the Myrf demyelination model.
- To test the hypothesis that spinal cord microglia dysfunction limits remyelination due to impaired phagocytosis or neuroinflammation.
Main Methods:
- Utilized the inducible, oligodendrocyte-specific knockout model of Myrf to induce demyelination in both brain and spinal cord.
- Characterized microglial phenotypes, including activation status, phagocytic marker expression, and morphology, during demyelination.
- Compared microglial responses in the brain versus the spinal cord.
Main Results:
- Brain microglia exhibited earlier activation and a higher percentage of phagocytic markers compared to spinal cord microglia.
- Spinal cord microglia displayed a delayed phagocytic response, sustained inflammation, and predominantly ameboid morphology.
- These findings suggest a primed and coordinated microglial response in the brain supporting remyelination.
Conclusions:
- Brain microglia mount a timely and effective response that facilitates remyelination following demyelination.
- Spinal cord microglia adopt a dysfunctional phenotype, characterized by delayed phagocytosis and persistent inflammation, which likely hinders myelin repair.
- Microglial dysfunction in the spinal cord may be a critical factor limiting remyelination in multiple sclerosis.
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