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Updated: Jan 9, 2026
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Published on: June 20, 2025
Cellular Communication Networks Mediated by Microglia in Ischemic Stroke
1Department of Neurology, Nanjing Drum Tower Hospital, Joint Institute of Nanjing Drum Tower Hospital for Life and Health, College of Life Science, Nanjing Normal University, Nanjing, China.
Introduction:
Microglia, the resident immune cells of the central nervous system, rapidly activate after ischemic stroke and actively communicate with neurons, astrocytes, endothelial cells, and infiltrating peripheral immune cells. As ischemic stroke remains a major cause of death and long-term disability worldwide, growing evidence highlights that microglia-driven communication-through direct cell-cell contact, soluble factors, and extracellular vesicles-plays a central role in regulating neuroinflammation and shaping disease progression. A clearer understanding of these communication networks may help identify new therapeutic strategies targeting glial function.
Methods:
This review summarizes recent advances in understanding microglial states after ischemic stroke and their communication with neural and peripheral immune cells. Literature was collected from PubMed and Web of Science, with attention to mechanisms involving direct cell-cell interaction, cytokine and chemokine signaling, extracellular vesicle communication, and newly described tunneling structures. Key regulatory processes at different pathological stages are compared.
Results:
Experimental and clinical evidence shows that microglia display dynamic and heterogeneous activation patterns after ischemic stroke. Through diverse communication pathways, they influence neuronal survival, synaptic remodeling, inflammatory responses, and blood-brain barrier integrity. Soluble mediators-including cytokines, chemokines, and damage-associated molecular patterns-shape both local and systemic immune reactions, while extracellular vesicles regulate neuroinflammation and tissue repair by transferring bioactive molecules. Recently reported microglial tunneling structures further increase the complexity of intercellular communication. Together, these pathways determine the progression of ischemic injury and recovery.
Conclusions:
Microglia act as central coordinators of communication among neurons, glial cells, and immune cells during ischemic stroke, thereby influencing disease severity and functional outcome. Clarifying microglia-mediated communication mechanisms may help guide the development of targeted immunomodulatory treatments. Continued research will be important for advancing these findings toward clinical translation.
Insights
Microglia coordinate cell communication after ischemic stroke, influencing recovery. Understanding these interactions offers new therapeutic targets for neuroinflammation and stroke outcomes.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are key immune cells in the central nervous system that activate post-ischemic stroke.
- They interact with various brain cells and peripheral immune cells, impacting stroke progression.
- Understanding these communication networks is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To review recent advancements in microglial states and communication after ischemic stroke.
- To explore mechanisms of microglial interaction, including cell-cell contact, soluble factors, and extracellular vesicles.
- To compare regulatory processes across different pathological stages of ischemic stroke.
Main Methods:
- Comprehensive literature review of studies on microglial activation and communication post-stroke.
- Analysis of mechanisms involving direct cell-cell interaction, cytokine/chemokine signaling, and extracellular vesicles.
- Examination of newly identified microglial tunneling structures.
Main Results:
- Microglia exhibit dynamic and heterogeneous activation patterns following ischemic stroke.
- Microglial communication pathways influence neuronal survival, synaptic plasticity, neuroinflammation, and blood-brain barrier integrity.
- Extracellular vesicles and tunneling nanotubes contribute to complex intercellular signaling, affecting injury and repair.
Conclusions:
- Microglia centrally coordinate intercellular communication, significantly impacting ischemic stroke severity and functional outcomes.
- Elucidating microglia-mediated communication pathways can guide the development of targeted immunomodulatory therapies.
- Further research is essential for translating these findings into clinical applications for stroke treatment.
