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Repertoire of microglial and macrophage responses after spinal cord injury

Nature Reviews Neuroscience volume 12, pages 388–399 (2011)Cite this article

Subjects

Key Points

  • Macrophages derived from the peripheral circulation and from resident microglia are among the main effectors of the inflammatory response after spinal cord injury.

  • Activated macrophages/microglia in the injured spinal cord contribute to secondary tissue damage through generation of reactive oxygen species, the production of pro-inflammatory cytokines and other factors. Macrophages under certain conditions also seem to have beneficial properties in the injured CNS.

  • Current understanding of macrophage polarization may provide better insights into why activated macrophages/microglia in the injured CNS have detrimental as well as beneficial properties.

  • Studies in the field of infectious disease, tumour biology and other non-neural systems indicate that macrophages can be polarized to a 'classically' activated M1 cell that is pro-inflammatory and cytotoxic, or to an 'alternatively' activated M2 cell that is anti-inflammatory and has reparative properties.

  • The microenvironment of the injured spinal cord favours polarization of M1 macrophages, with only a weak and transient M2 polarization.

  • Understanding how to put the brake on M1 polarization and promote M2 polarization in the injured spinal cord may lead to the development of novel therapeutic approaches for treating spinal cord injury.

Abstract

Macrophages from the peripheral circulation and those derived from resident microglia are among the main effector cells of the inflammatory response that follows spinal cord trauma. There has been considerable debate in the field as to whether the inflammatory response is good or bad for tissue protection and repair. Recent studies on macrophage polarization in non-neural tissues have shed much light on their changing functional states. In the context of this literature, we discuss the activation of macrophages and microglia following spinal cord injury, and their effects on repair. Harnessing their anti-inflammatory properties could pave the way for new therapeutic strategies for spinal cord trauma.

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Figure 1: Macrophages and microglia in the CNS.
Figure 2: M1 and M2 polarization.

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Acknowledgements

Work in the laboratory of S.D. has been funded by the Canadian Institutes of Health Research, the Multiple Sclerosis Society of Canada and the Wings for Life Spinal Cord Research Foundation.

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  1. Centre for Research in Neuroscience, The Research Institute of the McGill University Health Center, 1650 Cedar Avenue, Montreal, Quebec, Canada, H3G 1A4.,

    Samuel David & Antje Kroner

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Correspondence to Samuel David.

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Glossary

Polarized

Macrophages undergo a differentiation process driven by cytokines and other factors within the tissue microenvironment, and adopt pro- or anti-inflammatory phenotypes.

Zymosan-initiated peritonitis model

A model of inflammation produced by injecting zymosan, a protein–carbohydrate complex purified from yeast cell wall, into the peritoneal cavity.

Patrolling behaviour

Active movement of macrophages in the lumen of blood vessels, which may occur against the direction of blood flow.

Rolling behaviour

The first step in the process that leads to migration of immune cells from blood vessels into the surrounding tissue. Rolling involves low-strength adhesion of the cells to the inner surface of endothelial cells. This reduces the velocity at which they travel within the blood vessel.

Glial–fibrotic scar

A breach — however small — in the glial limitans that lines the outer edge of the spinal cord results in the proliferation and influx of meningeal fibroblasts and astrocytes. This glial–fibrotic interface forms an exaggerated version of the glia limitans at the injury site.

Secondary damage

Damage to neurons, axons, oligodendrocytes, myelin and astrocytes subsequent to the initial trauma. Secondary damage is induced by a variety of factors including ischaemia, pro-inflammatory cytokines, glutamate and free radicals.

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David, S., Kroner, A. Repertoire of microglial and macrophage responses after spinal cord injury. Nat Rev Neurosci 12, 388–399 (2011). https://doi.org/10.1038/nrn3053

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