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Updated: May 11, 2026
Intravital Imaging of Axonal Interactions with Microglia and Macrophages in a Mouse Dorsal Column Crush Injury
Published on: November 23, 2014
Temporal changes in monocyte and macrophage subsets and microglial macrophages following spinal cord injury in the
Sakina G Thawer1, Leah Mawhinney, Kristin Chadwick
1BioTherapeutics Research Laboratories and Spinal Cord Injury Team, Robarts Research Institute, 100 Perth Drive, London, Ontario, Canada, N6A 5K8.
Abstract:
The role of hematogenous (hMΦ) and microglial (mMΦ) macrophages following spinal cord injury (SCI) remains unclear as they are not distinguished easily from each other in the lesion area. We have recently described the temporal and spatial response to SCI of each MΦ population using the lys-EGFP-ki mouse that enables EGFP(+) hMΦ to be distinguished from EGFP(-) mMΦ at the lesion site. In the present study, we characterized the response of monocyte and hMΦ subsets and mMΦ to SCI. We describe, for the first time, the responses of circulating classical (pro-inflammatory) and non-classical monocyte subsets to SCI. Additionally, we show the presence of classical and non-classical hMΦ at the SCI lesion. Importantly, we demonstrate that the 'classical pro-inflammatory' hMΦ respond in the acute (1d, 3d) stages of SCI while the 'non-classical' hMΦ respond in the sub-acute (7d, 14d) phase of SCI. At later time points (6weeks post injury) classical hMΦ return to the injury site. Our study offers new insight into the cellular inflammatory response that occurs after SCI and suggests that the timing and targets of anti-inflammatory therapies may be crucial to maximize neuroprotection at the acute and more chronic stages of SCI.
Insights
Hematogenous and microglial macrophages play distinct roles after spinal cord injury (SCI). This study differentiates their responses, revealing specific timing for classical and non-classical macrophage subsets to optimize neuroprotection therapies.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Distinguishing between hematogenous (hMΦ) and microglial (mMΦ) macrophages in spinal cord injury (SCI) lesions is challenging.
- Previous work established methods to differentiate these macrophage populations using the lys-EGFP-ki mouse model.
Purpose of the Study:
- To characterize the distinct temporal and spatial responses of monocyte and macrophage subsets, including classical and non-classical hMΦ and mMΦ, following SCI.
- To elucidate the inflammatory cellular response dynamics in the acute and chronic phases post-SCI.
Main Methods:
- Utilized the lys-EGFP-ki mouse model to distinguish EGFP(+) hMΦ from EGFP(-) mMΦ.
- Characterized circulating classical and non-classical monocyte subsets and their presence as hMΦ within the SCI lesion.
- Analyzed macrophage responses at acute (1d, 3d), sub-acute (7d, 14d), and chronic (6 weeks) time points post-injury.
Main Results:
- Demonstrated distinct temporal responses: classical pro-inflammatory hMΦ are prominent in acute SCI stages (1-3 days), while non-classical hMΦ dominate the sub-acute phase (7-14 days).
- Observed the return of classical hMΦ to the injury site at later chronic stages (6 weeks post-injury).
- First-time characterization of circulating classical and non-classical monocyte subset responses to SCI.
Conclusions:
- The study provides novel insights into the complex cellular inflammatory response following SCI.
- Timing and targeting of anti-inflammatory therapies are critical for maximizing neuroprotection in both acute and chronic SCI phases.
