Related Experiment Video
Updated: Nov 20, 2025
Identifying Microglia and Peripheral Infiltrating Macrophages in the Injured Spinal Cords Using Flow Cytometry
Published on: June 24, 2025
Macrophage migration inhibitory factor as a therapeutic target after traumatic spinal cord injury: a systematic
Seyed Mohammad Piri1,2, Zahra Ghodsi1, Sina Shool1,3
1Sina Trauma and Surgery Research Center, Sina Hospital, Tehran University of Medical Sciences, Hassan-Abad Square, Imam Khomeini Ave, 11365-3876, Tehran, Iran.
Purpose:
Macrophages play an important role in mediating damage after Spinal cord injury (SCI) by secreting macrophage migration inhibitory factor (MMIF) as a secondary injury mediator. We aimed to systematically review the role of MMIF as a therapeutic target after traumatic SCI.
Methods:
Our systematic review has been performed according to the PRISMA 2009 Checklist. A systematic search in the scientific databases was carried out for studies published before 20 February 2019 from major databases. Two researchers independently screened titles. The risk of bias of eligible articles was assessed, and data were extracted. Finally, we systematically analyzed and interpreted related data.
Results:
785 papers were selected for the title and abstract screening. 12 papers were included for data extraction. Eight animal studies were of high quality and the remaining two were of medium quality. One of the two human studies was of poor quality and the other was of fair quality. MMIF as a pro-inflammatory mediator can cause increased susceptibility to glutamate-related neurotoxicity, increased nitrite production, increased ERK activation, and increased COX2/PGE2 signaling pathway activation and subsequent stimulation of CCL5-related chemotaxis. Two human studies and six animal studies demonstrated that MMIF level increases after SCI. MMIF inhibition might be a potential therapeutic target in SCI by multiple different mechanisms (6/12 studies).
Conclusion:
Most animal studies demonstrate significant neurologic improvement after administration of MMIF inhibitors, but these inhibitors have not been studied in humans yet. Further clinical trials are need to further understand MMIF inhibitor utility in acute or chronic SCI.
Level Of Evidence I:
Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.
Insights
Macrophage migration inhibitory factor (MMIF) contributes to secondary damage after spinal cord injury (SCI). Inhibiting MMIF shows therapeutic potential in animal models, but human studies are needed to confirm its efficacy for SCI treatment.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Macrophages are key mediators of secondary injury following spinal cord injury (SCI).
- Macrophage migration inhibitory factor (MMIF) is secreted by macrophages and acts as a pro-inflammatory mediator contributing to SCI pathogenesis.
- MMIF's role in SCI suggests it as a potential therapeutic target.
Purpose of the Study:
- To systematically review the scientific literature on the role of MMIF as a therapeutic target in traumatic spinal cord injury.
- To evaluate the evidence for MMIF's involvement in SCI pathophysiology and its potential as a treatment target.
Main Methods:
- A systematic literature search was conducted across major scientific databases for studies published before February 20, 2019.
- Studies were screened by two independent researchers, and eligible articles underwent risk of bias assessment and data extraction.
- Data were systematically analyzed and interpreted to synthesize findings on MMIF in SCI.
Main Results:
- 12 studies were included after screening 785 papers. Animal studies were generally of high quality, while human studies varied in quality.
- Elevated MMIF levels were observed after SCI in both human and animal studies.
- MMIF promotes neuroinflammation and neurotoxicity through pathways including glutamate excitotoxicity, nitrite production, ERK activation, and COX2/PGE2 signaling.
Conclusions:
- MMIF inhibition presents a potential therapeutic strategy for SCI, supported by findings in multiple studies.
- Animal studies indicate significant neurological improvement with MMIF inhibitors.
- Further clinical trials are essential to validate the utility of MMIF inhibitors in human acute or chronic SCI.
More Related Videos
08:43Intravital Imaging of Axonal Interactions with Microglia and Macrophages in a Mouse Dorsal Column Crush Injury
Published on: November 23, 2014
08:52Neuron-Macrophage Co-cultures to Activate Macrophages Secreting Molecular Factors with Neurite Outgrowth Activity
Published on: March 30, 2018