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Updated: Oct 1, 2025
Harnessing the Power of MicroRNA Cargoes in Small Extracellular Vesicles Released from Fresh-Frozen Human Brain Sections
Published on: November 8, 2024
Alterations of microRNAs expression profiles in small extracellular vesicle after traumatic brain injury in mice
Ye Tian1, Ruiting Zhao2, Xiaochun Li3
1Department of Neurosurgery, General Hospital, Tianjin Neurological Institute, Tianjin Medical University, No. 154, Anshan Road, Heping District, Tianjin, 300052, P.R. China.
Abstract:
Traumatic brain injury (TBI) is one of the leading causes of mortality and morbidity worldwide. Tools available for diagnosis and therapy are limited. Small extracellular vesicle (sEV) microRNAs (miRNAs) play an important role in TBI disease progression. This study aimed to investigate the alterations in sEV miRNAs expression in the mouse brain extracellular space after TBI. Twenty-four C57BL/6J mice were randomly divided into two groups (12/group). The TBI group was subjected to all surgical procedures and fluid percussion injury (FPI). The sham group only underwent surgery. Brain specimens were collected 3 h after TBI/sham. The brain sEV were isolated. Differentially expressed miRNAs were identified. A total of 50 miRNAs were observed to be differentially expressed (fold change ≥1.5 and P<0.05) after TBI, including 5 upregulated and 45 downregulated. The major enriched Gene Ontology terms were metabolic processes, cell, intracellular, organelle, cytoplasm, axon, binding, protein kinase activity, protein binding, and protein dimerization activity. The KEGG pathway analysis predicted that the pathways affected by the variation of miRNAs in sEVs after TBI included the Wnt signaling pathway and NF-κB signaling pathway. The changes in five miRNAs were confirmed by qRT-PCR. In conclusion, this study demonstrated the differential expression of a series of miRNAs in brain sEV after TBI, which might be correlated with post-TBI physiological and pathological processes. The findings might also provide novel targets for further investigating the molecular mechanisms underlying TBI and potential therapeutic interventions.
Insights
Traumatic brain injury (TBI) alters small extracellular vesicle (sEV) microRNAs (miRNAs) in the brain. These changes in brain sEV miRNAs may offer new insights into TBI mechanisms and potential therapies.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Traumatic brain injury (TBI) is a significant global health concern with limited diagnostic and therapeutic options.
- Small extracellular vesicles (sEVs) and their encapsulated microRNAs (miRNAs) are increasingly recognized for their roles in intercellular communication and disease pathogenesis, including TBI.
Purpose of the Study:
- To investigate the differential expression profiles of miRNAs within brain sEVs following experimental TBI.
- To identify specific miRNAs and associated biological pathways altered in the brain extracellular space post-TBI.
Main Methods:
- Induction of TBI using fluid percussion injury (FPI) in a mouse model (C57BL/6J).
- Isolation and characterization of brain small extracellular vesicles (sEVs).
- High-throughput sequencing and qRT-PCR to identify and validate differentially expressed miRNAs.
Main Results:
- A total of 50 miRNAs were found to be differentially expressed in brain sEVs 3 hours after TBI (5 upregulated, 45 downregulated).
- Enriched Gene Ontology terms included metabolic processes, cellular components (intracellular, organelle, cytoplasm, axon), and molecular functions (binding, protein kinase activity).
- KEGG pathway analysis implicated the Wnt and NF-κB signaling pathways in response to TBI-induced miRNA alterations.
Conclusions:
- TBI significantly alters the miRNA content of brain sEVs, suggesting their involvement in post-TBI physiological and pathological processes.
- The identified differentially expressed miRNAs and affected pathways represent potential biomarkers for TBI diagnosis and targets for therapeutic intervention.
