Related Experiment Video
Updated: Jul 25, 2026
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Exosomes miR-369-3p Alleviates Early Brain Injury After Subarachnoid Hemorrhage by Promoting Ferroptosis of M1
Jian Fang1, Feiyun Qin1, Pengcheng Xu2
1Department of Neurosurgery, The Translational Research Institute for Neurological Disorders of Wannan Medical College, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, China.
Background:
Ferroptosis in pathophysiological mechanisms in early brain injury after subarachnoid hemorrhage (SAH-EBI) has been demonstrated. MicroRNAs (miRNAs) are involved in various aspects of neurological disorders. A growing number of studies suggest that intense inflammation mediated by M1 microglia after subarachnoid hemorrhage (SAH) may lead to neurological damage. According to our research and related reports, exosomal miR-369-3p is involved in the pathophysiological process of SAH, and miR-369-3p has a potentially central role in regulating inflammatory responses. Therefore, targeted delivery of miR-369-3p across the blood-brain barrier (BBB) into the brain to alleviate SAH-EBI is a promising therapeutic approach.
Methods:
In this study, we extracted exosomes from RBCs and then modified RVG peptide onto the exosome surface using the click chemistry principle. Finally, miR-369-3p mimic was loaded into the RVG peptide-modified exosomes to form RVG-Exo/miR-369-3p (RVG-Exo/miR) by electroporation. Tail vein injection of RVG-Exo/miR was used to achieve delivery of miR-369-3p into the brain of SAH mice. The effect of miR-369-3p on SAH-EBI was examined by neurobehavioral scores, brain water content, Fluoro-Jade C (FJC) staining, and Nissl staining. MDA and GSH kits were used to assess the extent of ferroptosis occurrence. Western blotting analysis, immunofluorescence staining, and qRT-PCR were used to detect the levels of each protein, mRNA, and miRNA.
Results:
The exosome system (RVG-Exo/miR) successfully delivered miR-369-3p to the mouse central nervous system across the blood-brain barrierBBB. This exosomal system reduced the number of M1 microglia by enhancing their sensitivity to ferroptosis by inhibiting the expression of iNOS and GPX4. In addition, miR-369-3p treatment alleviated neurobehavioral disorders, brain edema, and neuronal damage after SAH-EBI.
Conclusions:
RVG-Exo/miR promotes ferroptosis in M1 microglia by inhibiting the iNOS/GPX4 axis, which may be a new and effective therapeutic strategy for treating SAH-EBI.
Insights
This study shows that engineered exosomes carrying miR-369-3p can cross the blood-brain barrier to treat early brain injury after subarachnoid hemorrhage. The treatment reduces M1 microglia-mediated inflammation and neuronal damage by promoting ferroptosis.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Molecular Biology
Background:
- Ferroptosis plays a role in early brain injury following subarachnoid hemorrhage (SAH-EBI).
- MicroRNAs (miRNAs) are implicated in neurological disorders, with exosomal miR-369-3p potentially regulating inflammation in SAH.
- Targeted delivery of miR-369-3p across the blood-brain barrier (BBB) offers a promising therapeutic strategy for SAH-EBI.
Purpose of the Study:
- To investigate the therapeutic potential of exosome-mediated delivery of miR-369-3p for SAH-EBI.
- To explore the mechanism by which miR-369-3p affects M1 microglia and ferroptosis in the context of SAH.
Main Methods:
- Exosomes were modified with RVG peptide and loaded with miR-369-3p mimic (RVG-Exo/miR).
- RVG-Exo/miR was administered via tail vein injection to SAH mice to facilitate BBB crossing.
- Neurobehavioral outcomes, brain water content, neuronal damage, and ferroptosis markers were assessed.
Main Results:
- RVG-Exo/miR successfully delivered miR-369-3p into the mouse central nervous system.
- Treatment reduced M1 microglia by promoting ferroptosis via inhibition of iNOS and GPX4.
- miR-369-3p administration alleviated neurobehavioral deficits, brain edema, and neuronal injury.
Conclusions:
- RVG-Exo/miR promotes M1 microglia ferroptosis by inhibiting the iNOS/GPX4 axis.
- This approach represents a novel and effective therapeutic strategy for SAH-EBI.
Related Concept Videos
01:22MicroRNAs
01:22MicroRNAs