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Updated: Apr 5, 2026

Identifying Microglia and Peripheral Infiltrating Macrophages in the Injured Spinal Cords Using Flow Cytometry
Published on: June 24, 2025
Age decreases macrophage IL-10 expression: Implications for functional recovery and tissue repair in spinal cord
Bei Zhang1, William M Bailey1, Kaitlyn J Braun1
1Spinal Cord and Brain Injury Research Center, Department of Physiology, University of Kentucky, Lexington, KY 40536, United States.
Abstract:
Macrophages with different activation states are present after spinal cord injury (SCI). M1 macrophages purportedly promote secondary injury processes while M2 cells support axon growth. The average age at the time of SCI has increased in recent decades, however, little is known about how different physiological factors contribute to macrophage activation states after SCI. Here we investigate the effect of age on IL-10, a key indicator of M2 macrophage activation. Following mild-moderate SCI in 4 and 14 month old (MO) mice we detected significantly reduced IL-10 expression with age in the injured spinal cord. Specifically, CD86/IL-10 positive macrophages, also known as M2b or regulatory macrophages, were reduced in 14 vs. 4 MO SCI animals. This age-dependent shift in macrophage phenotype was associated with impaired functional recovery and enhanced tissue damage in 14-month-old SCI mice. In vitro, M2b macrophages release anti-inflammatory cytokines without causing neurotoxicity, suggesting that imbalances in the M2b response in 14-month-old mice may be contributing to secondary injury processes. Our data indicate that age is an important factor that regulates SCI inflammation and recovery even to mild-moderate injury. Further, alterations in macrophage activation states may contribute to recovery and we have identified the M2b phenotype as a potential target for therapeutic intervention.
Insights
Aging impairs spinal cord injury (SCI) recovery by reducing beneficial M2b macrophages. This age-related shift in immune response exacerbates damage and hinders functional outcomes after SCI.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Spinal cord injury (SCI) involves complex immune responses with M1 macrophages promoting injury and M2 macrophages aiding recovery.
- Increasing average age at SCI necessitates understanding how physiological factors like aging influence macrophage activation.
- Interleukin-10 (IL-10) is a key marker for M2 macrophage activation, crucial for anti-inflammatory responses.
Purpose of the Study:
- To investigate the impact of aging on macrophage activation states, specifically IL-10 expression, following SCI.
- To determine if age influences the abundance of M2b (regulatory) macrophages after SCI.
- To correlate age-dependent changes in macrophage phenotype with functional recovery and tissue damage post-SCI.
Main Methods:
- Induction of mild-moderate SCI in young (4-month-old) and aged (14-month-old) mice.
- Quantification of IL-10 expression and CD86/IL-10 positive (M2b) macrophages in injured spinal cord tissue.
- Assessment of functional recovery and histological analysis of tissue damage.
- In vitro studies of M2b macrophage-derived cytokines and neurotoxicity.
Main Results:
- A significant age-dependent reduction in IL-10 expression was observed in the injured spinal cord of older mice.
- The population of CD86/IL-10 positive (M2b) macrophages was significantly lower in 14-month-old SCI mice compared to 4-month-old mice.
- Reduced M2b macrophage presence in aged mice correlated with impaired functional recovery and increased secondary tissue damage.
- In vitro, M2b macrophages exhibited anti-inflammatory properties without neurotoxicity.
Conclusions:
- Age is a critical factor modulating the inflammatory response and recovery outcomes after SCI, even following mild to moderate injuries.
- The age-related decrease in M2b macrophage activation may contribute to heightened secondary injury processes and poorer functional recovery.
- The M2b macrophage phenotype represents a potential therapeutic target for improving SCI outcomes in aged individuals.
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