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Updated: Oct 11, 2025
Triggering Reactive Gliosis In Vivo by a Forebrain Stab Injury
Published on: June 29, 2015
Stroke subtype-dependent synapse elimination by reactive gliosis in mice
Xiaojing Shi1, Longlong Luo1,2, Jixian Wang3
1School of Biomedical Engineering and Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China.
Abstract:
The pathological role of reactive gliosis in CNS repair remains controversial. In this study, using murine ischemic and hemorrhagic stroke models, we demonstrated that microglia/macrophages and astrocytes are differentially involved in engulfing synapses in the reactive gliosis region. By specifically deleting MEGF10 and MERTK phagocytic receptors, we determined that inhibiting phagocytosis of microglia/macrophages or astrocytes in ischemic stroke improved neurobehavioral outcomes and attenuated brain damage. In hemorrhagic stroke, inhibiting phagocytosis of microglia/macrophages but not astrocytes improved neurobehavioral outcomes. Single-cell RNA sequencing revealed that phagocytosis related biological processes and pathways were downregulated in astrocytes of the hemorrhagic brain compared to the ischemic brain. Together, these findings suggest that reactive microgliosis and astrogliosis play individual roles in mediating synapse engulfment in pathologically distinct murine stroke models and preventing this process could rescue synapse loss.
Insights
Reactive gliosis in CNS repair is debated. Inhibiting synapse engulfment by microglia/macrophages or astrocytes improved outcomes in ischemic stroke, while only microglia/macrophages benefited in hemorrhagic stroke, suggesting targeted therapies.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- The role of reactive gliosis in central nervous system (CNS) repair is not fully understood.
- Reactive gliosis involves glial cells like microglia/macrophages and astrocytes responding to injury.
- Synapse engulfment by these reactive glial cells is a key process in CNS repair.
Purpose of the Study:
- To investigate the differential roles of microglia/macrophages and astrocytes in synapse engulfment during CNS repair.
- To determine the pathological significance of MEGF10 and MERTK phagocytic receptors in stroke models.
- To explore therapeutic strategies targeting glial phagocytosis for stroke recovery.
Main Methods:
- Utilized murine models of ischemic and hemorrhagic stroke.
- Genetically deleted MEGF10 and MERTK phagocytic receptors in microglia/macrophages and astrocytes.
- Assessed neurobehavioral outcomes and brain damage.
- Performed single-cell RNA sequencing to analyze cellular pathways.
Main Results:
- In ischemic stroke, inhibiting phagocytosis by either microglia/macrophages or astrocytes improved outcomes and reduced brain damage.
- In hemorrhagic stroke, inhibiting microglia/macrophage phagocytosis improved outcomes, but astrocyte phagocytosis inhibition did not.
- Single-cell RNA sequencing showed downregulated phagocytosis pathways in astrocytes from hemorrhagic brains compared to ischemic brains.
Conclusions:
- Reactive microgliosis and astrogliosis have distinct roles in synapse engulfment in different stroke types.
- Targeting microglia/macrophage phagocytosis shows therapeutic potential for both ischemic and hemorrhagic stroke.
- Preventing synapse engulfment by reactive glial cells can rescue synapse loss and improve recovery.
