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Published on: June 20, 2025
Neuroprotective Effect of Macrophage Migration Inhibitory Factor (MIF) in a Mouse Model of Ischemic Stroke
Ji Ae Kim1, Ye Young Kim2, Seung Hak Lee1
1Asan Medical Center, Department of Rehabilitation Medicine, University of Ulsan College of Medicine, Seoul 05505, Korea.
Abstract:
The mechanism of the neuroprotective effect of the macrophage migration inhibitory factor (MIF) in vivo is unclear. We investigated whether the MIF promotes neurological recovery in an in vivo mouse model of ischemic stroke. Transient middle cerebral artery occlusion (MCAO) surgery was performed to make ischemic stroke mouse model. Male mice were allocated to a sham vehicle, a sham MIF, a middle cerebral artery occlusion (MCAO) vehicle, and MCAO+MIF groups. Transient MCAO (tMCAO) was performed in the MCAO groups, and the vehicle and the MIF were administered via the intracerebroventricular route. We evaluated the neurological functional scale, the rotarod test, and T2-weighted magnetic resonance imaging. The expression level of the microtubule-associated protein 2 (MAP2), Bcl2, and the brain-derived neurotrophic factor (BDNF) were further measured by Western blot assay. The Garcia test was significantly higher in the MCAO+MIF group than in the MCAO+vehicle group. The MCAO+MIF group exhibited significantly better performance on the rotarod test than the MCAO+vehicle group, which further had a significantly reduced total infarct volume on T2-weighted MRI imaging than the MCAO vehicle group. Expression levels of BDNF, and MAP2 tended to be higher in the MCAO+MIF group than in the MCAO+vehicle group. The MIF exerts a neuroprotective effect in an in vivo ischemic stroke model. The MIF facilitates neurological recovery and protects brain tissue from ischemic injury, indicating a possibility of future novel therapeutic agents for stroke patients.
Insights
Macrophage migration inhibitory factor (MIF) administration improved neurological recovery and reduced brain injury in a mouse model of ischemic stroke. MIF shows potential as a therapeutic agent for stroke patients.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- The neuroprotective mechanisms of macrophage migration inhibitory factor (MIF) in vivo remain largely unelucidated.
- Ischemic stroke poses a significant global health challenge with limited effective treatments.
Purpose of the Study:
- To investigate the efficacy of macrophage migration inhibitory factor (MIF) in promoting neurological recovery and protecting brain tissue in a mouse model of ischemic stroke.
Main Methods:
- An in vivo mouse model of ischemic stroke was established using transient middle cerebral artery occlusion (MCAO).
- Mice were administered MIF or vehicle intracerebroventricularly.
- Neurological function was assessed using the Garcia test and rotarod test.
- Brain infarct volume was quantified using T2-weighted MRI.
- Expression of microtubule-associated protein 2 (MAP2) and brain-derived neurotrophic factor (BDNF) was analyzed via Western blot.
Main Results:
- MIF administration significantly improved neurological function scores in the Garcia test and rotarod test compared to vehicle-treated MCAO mice.
- T2-weighted MRI revealed a significant reduction in infarct volume in the MCAO+MIF group.
- Expression levels of BDNF and MAP2 showed a trend toward increase in the MCAO+MIF group.
Conclusions:
- Macrophage migration inhibitory factor (MIF) exerts significant neuroprotective effects in an in vivo model of ischemic stroke.
- MIF administration facilitates neurological recovery and mitigates ischemic brain injury.
- MIF represents a promising therapeutic candidate for future stroke treatments.

