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Updated: Jan 9, 2026
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
KLF2-mediated activation of Nrf2-HO-1 pathway modulates microglia/macrophage polarization post-ischemic stroke
Gui-Yuan Huang1, Hong-Miao Tao1, Yuan-Yuan Wu1
1Medical College, Jinhua University of Vocational Technology, Jinhua, China.
Background:
Shifting the microglia/macrophages from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype shows promise in developing therapeutic strategies after ischemic stroke (IS). The study is aimed to investigate the role of krueppel-like factor 2 (KLF2) in modulating microglia/macrophage polarization during IS.
Methods:
Mice received a 60-min middle cerebral artery occlusion (MCAO) and BV-2 cells underwent oxygen-glucose deprivation/reperfusion (OGD/R) treatment to induce IS-like injury in vivo and in vitro.
Results:
The mice subjected to MCAO exhibited impaired neurobehavioral performance, lower expressions of KLF2, Nrf2 and HO-1 in the peri-infarct cortex than the sham operated mice. Lentivirus-mediated KLF2 overexpression could effectively reduce the size of brain infarct, improve the recovery of neurobehavioral functions, and activate the Nrf2-HO-1 pathway in the mice subjected to MCAO. In addition, KLF2 overexpression led to M1 suppression and increase in M2 phenotype in OGD/R-insulted BV-2 microglial cells. Nrf2 knockdown was found to impair the effects of KLF2 overexpression on status of M1 and M2 phenotypes in OGD/R-insulted BV-2 cells.
Conclusion:
The study unveils KLF2 is neuroprotection and could promote microglia/macrophage polarization from the M1 to M2 phenotype in IS by activating the Nrf2-HO-1 pathway.
Insights
Krueppel-like factor 2 (KLF2) promotes neuroprotection in ischemic stroke (IS) by shifting microglia/macrophages to an anti-inflammatory M2 phenotype. This involves activating the Nrf2-HO-1 pathway, offering a promising therapeutic strategy for IS.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Ischemic stroke (IS) treatment strategies aim to modulate microglia/macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotypes.
- Krueppel-like factor 2 (KLF2) is investigated for its role in regulating this polarization during IS.
Purpose of the Study:
- To investigate the role of krueppel-like factor 2 (KLF2) in modulating microglia/macrophage polarization during ischemic stroke (IS).
Main Methods:
- Ischemic stroke (IS)-like injury was induced in mice via middle cerebral artery occlusion (MCAO) and in BV-2 cells using oxygen-glucose deprivation/reperfusion (OGD/R).
- Lentivirus-mediated KLF2 overexpression was employed in vivo and in vitro models.
Main Results:
- MCAO mice showed impaired neurobehavior, reduced KLF2, Nrf2, and HO-1 expression.
- KLF2 overexpression reduced infarct size, improved neurobehavioral recovery, and activated the Nrf2-HO-1 pathway.
- KLF2 overexpression suppressed M1 and increased M2 phenotypes in OGD/R-treated BV-2 cells, an effect blunted by Nrf2 knockdown.
Conclusions:
- KLF2 exhibits neuroprotective effects in ischemic stroke (IS).
- KLF2 promotes microglia/macrophage polarization from M1 to M2 phenotypes via the Nrf2-HO-1 pathway.
- KLF2 represents a potential therapeutic target for ischemic stroke.
