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Updated: Nov 21, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglia exosomal miRNA-137 attenuates ischemic brain injury through targeting Notch1
Dianquan Zhang1, Guoliang Cai2,3, Kai Liu4
1Department of Rehabilitation Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, China.
Abstract:
Microglia are the resident immune cells in the central nervous system and play an essential role in brain homeostasis and neuroprotection in brain diseases. Exosomes are crucial in intercellular communication by transporting bioactive miRNAs. Thus, this study aimed to investigate the function of microglial exosome in the presence of ischemic injury and related mechanism. Oxygen-glucose deprivation (OGD)-treated neurons and transient middle cerebral artery occlusion (TMCAO)-treated mice were applied in this study. Western blotting, RT-PCR, RNA-seq, luciferase reporter assay, transmission electron microscope, nanoparticle tracking analysis, immunohistochemistry, TUNEL and LDH assays, and behavioral assay were applied in mechanistic and functional studies. The results demonstrated that exosomes derived from microglia in M2 phenotype (BV2-Exo) were internalized by neurons and attenuated neuronal apoptosis in response to ischemic injury in vitro and in vivo. BV2-Exo also decreased infarct volume and behavioral deficits in ischemic mice. Exosomal miRNA-137 was upregulated in BV2-Exo and participated in the partial neuroprotective effect of BV2-Exo. Furthermore, Notch1 was a directly targeting gene of exosomal miRNA-137. In conclusion, these results suggest that BV2-Exo alleviates ischemia-reperfusion brain injury through transporting exosomal miRNA-137. This study provides novel insight into microglial exosomes-based therapies for the treatment of ischemic brain injury.
Insights
Microglial exosomes carrying miRNA-137 protect the brain from ischemic injury by reducing neuronal apoptosis. This finding offers a novel therapeutic strategy for treating brain ischemia.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are key immune cells in the central nervous system, vital for brain health.
- Exosomes mediate intercellular communication via microRNAs (miRNAs), influencing disease processes.
- Ischemic brain injury involves neuronal damage and requires effective therapeutic interventions.
Purpose of the Study:
- To investigate the neuroprotective role of microglial exosomes in ischemic brain injury.
- To elucidate the underlying molecular mechanisms, including miRNA involvement.
- To explore potential exosome-based therapeutic strategies for stroke.
Main Methods:
- Utilized oxygen-glucose deprivation (OGD) in neurons and transient middle cerebral artery occlusion (TMCAO) in mice.
- Employed techniques such as Western blotting, RT-PCR, RNA-seq, and electron microscopy.
- Assessed neuronal apoptosis, infarct volume, and behavioral deficits.
Main Results:
- Exosomes from M2-polarized microglia (BV2-Exo) reduced neuronal apoptosis and infarct volume in vitro and in vivo.
- BV2-Exo improved behavioral deficits in mice following ischemic injury.
- Exosomal miRNA-137 was upregulated and contributed to the neuroprotective effects by targeting Notch1.
Conclusions:
- Microglial-derived exosomes, specifically BV2-Exo, exert significant neuroprotection against ischemic brain injury.
- Exosomal miRNA-137 plays a crucial role in mediating these protective effects.
- This research highlights microglial exosomes as a promising therapeutic avenue for ischemic brain injury treatment.
