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Updated: Jun 1, 2025
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Curcumin Regulates Microglia Polarization to Alleviate Ischemic Stroke by Targeting microRNA-205-5p/Kruppel-Like
1Hunan University of Medicine, Huaihua, China.
Abstract:
Ischemic stroke (IS) often causes fearful sequela, even death. Curcumin was beneficial to IS, but its underlying molecular mechanism is unclear. Mice were subjected to middle cerebral artery occlusion (MCAO) surgery, and BV-2 cells were treated with oxygen-glucose deprivation/reoxygenation (OGD/R) induction to establish IS models in vivo and in vitro. Abundance of genes and proteins was determined using quantitative real-time polymerase chain reaction (RT-qPCR), immunofluorescence (IF), and western blot. Interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) levels were analyzed using enzyme-linked immunosorbent assay (ELISA). Modified neurological severity score (mNSS), corner test, foot fault test, adhesive removal test, and 2,3,5-triphenyltetrazolium chloride (TTC) staining were applied to evaluate the brain injury of mice. The correlation between miR-205-5p and Kruppel-like factor 2 (KLF2) was affirmed using dual luciferase reporter assay. Our results revealed that curcumin alleviated brain damage in MCAO mice through driving microglia M2 polarization. Of note, curcumin resulted in decreased miR-205-5p expression in MCAO mice. miR-205-5p knockdown resulted in promoted microglia M2 polarization in OGD/R conditions and achieved similar results to curcumin treatment in MCAO mice. Moreover, curcumin played a promoting role in microglia M2 polarization under OGD/R conditions, while miR-205-5p overexpression or KLF2 knockdown abolished these effects. On the mechanism, miR-205-5p was a target of curcumin, and miR-205-5p further interacted with KLF2 to inhibit activating transcription factor 2 (ATF2) expression. miR-205-5p, decreased by curcumin, suppressed microglia M2 polarization to worsen IS injury through the mediating KLF2/ATF2 axis.
Insights
Curcumin benefits ischemic stroke by promoting M2 microglia polarization. It reduces miR-205-5p, which normally inhibits this beneficial process via the KLF2/ATF2 pathway, thus alleviating brain damage.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Ischemic stroke (IS) is a leading cause of death and disability.
- Curcumin shows therapeutic potential for IS, but its molecular mechanisms remain elusive.
- Microglia polarization plays a critical role in IS pathogenesis.
Purpose of the Study:
- To elucidate the molecular mechanism by which curcumin alleviates ischemic stroke.
- To investigate the role of miR-205-5p and its interaction with KLF2/ATF2 in curcumin's neuroprotective effects.
Main Methods:
- Established in vivo (MCAO) and in vitro (OGD/R) models of ischemic stroke.
- Assessed gene and protein expression via RT-qPCR, IF, and Western blot.
- Measured cytokine levels (IL-1β, IL-6, IL-10) using ELISA and evaluated brain injury using behavioral tests and TTC staining.
Main Results:
- Curcumin treatment alleviated brain damage in MCAO mice by promoting M2 microglia polarization.
- Curcumin decreased miR-205-5p expression; miR-205-5p knockdown mimicked curcumin's protective effects.
- miR-205-5p targets KLF2, inhibiting the KLF2/ATF2 axis, and curcumin's effect on M2 polarization was abolished by miR-205-5p overexpression or KLF2 knockdown.
Conclusions:
- Curcumin exerts neuroprotection in ischemic stroke by downregulating miR-205-5p.
- This downregulation promotes M2 microglia polarization via the KLF2/ATF2 pathway, reducing brain injury.
- Curcumin's therapeutic effect is mediated through the miR-205-5p/KLF2/ATF2 axis, highlighting a novel therapeutic target for IS.
