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Updated: Sep 20, 2025
Author Spotlight: Establishing a Reliable Distal MCA Occlusion Model in Mice for Stroke Research
Published on: December 15, 2023
The antioxidant enzyme Peroxiredoxin-1 controls stroke-associated microglia against acute ischemic stroke
Sinai Kim1, Wonhyo Lee2, Huiju Jo1
1Heart-Immune-Brain Network Research Center, Department of Life Science, Ewha Womans University, Seoul, 03760, Republic of Korea.
Abstract:
Ischemic stroke is the leading cause of immortal disability and death worldwide. For treatment in the acute phase, it is necessary to control excessive reactive oxygen species (ROS) damage during ischemia/reperfusion (I/R). Microglia are well known to be closely associated with excessive ROS response in the early stage of I/R. However, the precise roles of microglia associated with mitigating ROS damage, and molecular markers of heterogenetic microglia in the I/R damaged brain has not been clarified. Here, we identified a new type of microglia associated with stroke in the I/R injured brain. Single-cell RNA sequencing (scRNA-seq) was used to assess transcriptional changes of microglia and immune cells in the contralateral (CL) and ipsilateral (IL) hemispheres after transient middle cerebral artery occlusion (tMCAO) surgery to mimic ischemic stroke. We classified a unique type of microglia with enhanced antioxidant function and markers similar to those of disease-associated microglia (DAM), designated them as stroke-associated microglia (SAM). The representative antioxidant enzyme, Peroxiredoxin-1 (Prdx1), was predominantly expressed in SAM and mediated ROS defense genes, including Txn1, Srx1, Mt1, and Mt2. In the Prdx1-/- I/R damaged brain, we observed significantly increased infarction, as assessed by TTC staining, and FACS analysis detected severe microglial cell death. Importantly, scRNA transcriptomics data showed that the SAM population was specifically decreased in Prdx1-/- mice and that these mice exhibited decreased ROS damage resistance. Inflammatory responses which were detected by ELISA and qPCR, were also increased in Prdx1-/- IL hemispheres. Finally, Prdx1-dependent antioxidative SAM were found to be essential for increasing the transcription levels of stroke-protective molecules, such as osteopontin and ferritin. A novel microglia type (SAM) is specifically activated in response to stroke I/R injury, and that Prdx1 expression is required for the activation and enhanced antioxidant function of SAM.
Insights
Researchers discovered stroke-associated microglia (SAM) that protect against reactive oxygen species (ROS) damage after ischemic stroke. Peroxiredoxin-1 (Prdx1) is crucial for SAM
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Ischemic stroke causes significant global disability and mortality.
- Controlling reactive oxygen species (ROS) damage during ischemia/reperfusion (I/R) is critical for acute stroke treatment.
- Microglia's role in ROS response and mitigation during I/R stroke is not fully understood.
Purpose of the Study:
- To identify novel microglia types involved in mitigating ROS damage in ischemic stroke.
- To characterize the molecular markers and functions of these unique microglia.
- To investigate the role of Peroxiredoxin-1 (Prdx1) in stroke-associated microglia (SAM) activation and function.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) to analyze microglia and immune cell transcriptomes after transient middle cerebral artery occlusion (tMCAO) in mice.
- Quantitative analysis of infarct volume using TTC staining and cell death using FACS analysis.
- ELISA and qPCR to assess inflammatory responses and gene expression.
Main Results:
- A novel microglia population, termed stroke-associated microglia (SAM), was identified with enhanced antioxidant functions.
- SAM predominantly express Peroxiredoxin-1 (Prdx1), which mediates ROS defense genes.
- Prdx1 deficiency in mice led to increased infarction, microglial cell death, reduced SAM populations, and heightened inflammation.
- Prdx1-dependent SAM are essential for upregulating stroke-protective molecules like osteopontin and ferritin.
Conclusions:
- A novel microglia type, SAM, is specifically activated in response to stroke I/R injury.
- Prdx1 expression is required for SAM activation and their enhanced antioxidant capacity.
- Targeting Prdx1-dependent SAM may offer a therapeutic strategy for ischemic stroke.
