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Updated: Nov 2, 2025
Isolation and Flow Cytometric Assessment of Neuroimmune Interactions in a Mini-Stroke Murine Model
Published on: June 20, 2025
Genome-Wide Screen and Validation of Microglia Pro-Inflammatory Mediators in Stroke
Jianhua Wu1,2,3, Zhuoze Wu1,2, Aodi He1,2
11Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract:
Stroke activates microglia pro-inflammatory response that not only induces the early neuronal injuries but also causes the secondary brain infarction. Yet, the underlying mechanisms for how microglia become activated in stroke are still unknown. Here, using the next-generation of RNA sequencing we find a total of 778 genes increasingly expressed in brain of stroke mice. Of these, we identified Hmgb2 as a microglia pro-inflammatory mediator by promoting the transcription of Ctss. Inhibition of either Hmgb2 or Ctss blocks microglia pro-inflammatory response and protects against brain damages and improves the neurological functions of stroke mice. This study uncovers Hmgb2 and Ctss as the major microglia inflammatory response mediators in stroke and hence warrants the promising targets for stroke therapies.
Insights
Stroke triggers brain inflammation via microglia activation. Researchers identified Hmgb2 and Ctss as key mediators, offering potential new therapeutic targets for stroke treatment and brain damage reduction.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Stroke induces a pro-inflammatory response in microglia, contributing to neuronal injury and secondary brain infarction.
- The precise mechanisms driving microglial activation during stroke remain largely unknown.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying microglial activation in stroke.
- To identify novel therapeutic targets for mitigating stroke-induced brain damage.
Main Methods:
- Utilized next-generation RNA sequencing to analyze gene expression in the brains of stroke-induced mice.
- Investigated the role of identified genes, specifically Hmgb2 and Ctss, in microglial activation and stroke pathology.
- Evaluated the therapeutic potential of inhibiting Hmgb2 or Ctss.
Main Results:
- Identified 778 genes with increased expression in the stroke mouse brain.
- Discovered that Hmgb2 acts as a pro-inflammatory mediator by promoting Ctss transcription in microglia.
- Demonstrated that inhibiting either Hmgb2 or Ctss significantly reduced microglial pro-inflammatory responses, protected against brain damage, and improved neurological function in stroke mice.
Conclusions:
- Hmgb2 and Ctss are identified as critical mediators of the microglial inflammatory response in stroke.
- Targeting Hmgb2 or Ctss presents a promising therapeutic strategy for stroke intervention.
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