Related Experiment Video
Updated: May 22, 2026
Identifying Microglia and Peripheral Infiltrating Macrophages in the Injured Spinal Cords Using Flow Cytometry
Published on: June 24, 2025
Microglial inhibitory factor (MIF/TKP) mitigates secondary damage following spinal cord injury
Jaime Emmetsberger1, Stella E Tsirka
1Program in Molecular and Cellular Pharmacology, Stony Brook University, Stony Brook, NY 11794‐8651, USA.
Abstract:
Spinal cord injury (SCI) induces an immune response during which microglia, the resident immunocompetent cells of the central nervous system, become activated and migrate to the site of damage. Depending on their state of activation, microglia secrete neurotoxic or neurotrophic factors that influence the surrounding environment and have a detrimental or restorative effect following SCI, including causing or protecting bystander damage to nearby undamaged tissue. Subsequent infiltration of macrophages contributes to the SCI outcome. We show here that suppressing microglia/macrophage activation using the tripeptide macrophage/microglia inhibitory factor (MIF/TKP) reduced secondary injury around the lesion epicenter in the murine dorsal hemisection model of SCI; it decreased the hypertrophic change of astrocytes and caused an increase in the number of axons present within the lesion epicenter. Moreover, timely inhibition of microglial/macrophage activation prevented demyelination and axonal dieback by modulating oligodendrocyte survival and oligodendrocyte precursor maturation. Microglia/macrophages located within or proximal to the lesion produced neurotoxic factors, such as tumor necrosis factor alpha (TNF-α). These results suggest that microglia/macrophages within the epicenter at early time points post injury are neurotoxic, contributing to demyelination and axonal degeneration and that MIF/TKP could be used in combination with other therapies to promote functional recovery.
Insights
Suppressing activated microglia and macrophages with MIF/TKP after spinal cord injury (SCI) reduced secondary damage, preserved axons, and prevented demyelination, suggesting therapeutic potential.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Spinal cord injury (SCI) triggers an immune response involving microglia and macrophages.
- Activated microglia/macrophages can secrete factors that are either neurotoxic or neurotrophic, influencing tissue damage and repair.
- These immune cells play a critical role in secondary injury progression and functional outcomes after SCI.
Purpose of the Study:
- To investigate the therapeutic potential of suppressing microglia/macrophage activation using the tripeptide macrophage/microglia inhibitory factor (MIF/TKP) in a murine model of SCI.
- To determine the effects of MIF/TKP on secondary injury, axonal integrity, astrogliosis, and myelination following SCI.
Main Methods:
- Utilized a murine dorsal hemisection model of spinal cord injury.
- Administered the tripeptide macrophage/microglia inhibitory factor (MIF/TKP) to suppress microglia and macrophage activation.
- Assessed secondary injury, astrogliosis, axonal count, demyelination, and oligodendrocyte survival/maturation post-injury.
Main Results:
- Suppression of microglia/macrophage activation with MIF/TKP significantly reduced secondary injury around the lesion epicenter.
- Treatment decreased hypertrophic changes in astrocytes and increased the number of axons within the lesion epicenter.
- Timely inhibition prevented demyelination and axonal dieback by positively modulating oligodendrocyte survival and precursor maturation. Neurotoxic factors like TNF-α were reduced.
Conclusions:
- Early-acting microglia/macrophages at the SCI epicenter contribute to neurotoxicity, demyelination, and axonal degeneration.
- MIF/TKP demonstrates neuroprotective effects by mitigating secondary injury and promoting axonal and myelin preservation.
- MIF/TKP holds promise as a therapeutic agent, potentially in combination with other treatments, to enhance functional recovery after spinal cord injury.
