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Updated: Jun 6, 2026
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Macrophage migration inhibitory factor promotes cell death and aggravates neurologic deficits after experimental
Ana R Inácio1, Karsten Ruscher, Lin Leng
1Department of Clinical Sciences, Laboratory for Experimental Brain Research, Lund University, Lund, Sweden. ana.inacio@med.lu.se
Abstract:
Multiple mechanisms contribute to tissue demise and functional recovery after stroke. We studied the involvement of macrophage migration inhibitory factor (MIF) in cell death and development of neurologic deficits after experimental stroke. Macrophage migration inhibitory factor is upregulated in the brain after cerebral ischemia, and disruption of the Mif gene in mice leads to a smaller infarct volume and better sensory-motor function after transient middle cerebral artery occlusion (tMCAo). In mice subjected to tMCAo, we found that MIF accumulates in neurons of the peri-infarct region, particularly in cortical parvalbumin-positive interneurons. Likewise, in cultured cortical neurons exposed to oxygen and glucose deprivation, MIF levels increase, and inhibition of MIF by (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) protects against cell death. Deletion of MIF in Mif(-/-) mice does not affect interleukin-1β protein levels in the brain and serum after tMCAo. Furthermore, disruption of the Mif gene in mice does not affect CD68, but it is associated with higher galectin-3 immunoreactivity in the brain after tMCAo, suggesting that MIF affects the molecular/cellular composition of the macrophages/microglia response after experimental stroke. We conclude that MIF promotes neuronal death and aggravates neurologic deficits after experimental stroke, which implicates MIF in the pathogenesis of neuronal injury after stroke.
Insights
Macrophage migration inhibitory factor (MIF) worsens stroke outcomes by increasing neuronal death and neurological deficits. Reducing MIF levels in experimental stroke models improved recovery and reduced infarct size.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Stroke causes significant neuronal damage and functional deficits.
- Macrophage migration inhibitory factor (MIF) is implicated in inflammatory responses and cell death pathways.
- Understanding the role of specific molecules like MIF in stroke pathogenesis is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of macrophage migration inhibitory factor (MIF) in neuronal cell death and functional recovery following experimental stroke.
- To determine the impact of MIF gene disruption on infarct volume and sensory-motor deficits after transient middle cerebral artery occlusion (tMCAo).
Main Methods:
- Utilized a transient middle cerebral artery occlusion (tMCAo) model in mice.
- Examined MIF expression in neurons, particularly parvalbumin-positive interneurons, in the peri-infarct region.
- Investigated the effect of MIF inhibition using ISO-1 in cultured neurons subjected to oxygen-glucose deprivation.
- Assessed the impact of Mif gene deletion on inflammatory markers (Interleukin-1β, CD68, galectin-3) post-stroke.
Main Results:
- Mice lacking the Mif gene exhibited smaller infarct volumes and improved sensory-motor function after tMCAo.
- MIF was found to accumulate in neurons within the peri-infarct area.
- Inhibition of MIF protected cultured neurons from oxygen-glucose deprivation-induced cell death.
- MIF deficiency altered the macrophage/microglia response, indicated by changes in galectin-3 immunoreactivity, without affecting Interleukin-1β or CD68 levels.
Conclusions:
- Macrophage migration inhibitory factor (MIF) plays a detrimental role in stroke by promoting neuronal death and exacerbating neurological deficits.
- Targeting MIF presents a potential therapeutic strategy for mitigating neuronal injury and improving outcomes after ischemic stroke.
