The Role of Microglial Exosomes and miR-124-3p in Neuroinflammation and Neuronal Repair after Traumatic Brain Injury

Author:

Mavroudis Ioannis12,Balmus Ioana-Miruna3,Ciobica Alin4567,Nicoara Mircea Nicusor48ORCID,Luca Alina Costina9ORCID,Palade Dragos Octavian9ORCID

Affiliation:

1. Department of Neurology, Leeds Teaching Hospitals, NHS Trust, Leeds LS2 9JT, UK

2. Faculty of Medicine, Leeds University, Leeds LS2 9JT, UK

3. Department of Exact Sciences and Natural Sciences, Institute of Interdisciplinary Research, Alexandru Ioan Cuza University of Iasi, Str. Alexandru Lapusneanu, no. 26, 700057 Iasi, Romania

4. Department of Biology, Faculty of Biology, Alexandru Ioan Cuza University of Iasi, Bd. Carol I no. 20A, 700505 Iasi, Romania

5. Centre of Biomedical Research, Romanian Academy, Bd. Carol I, no. 8, 700506 Iasi, Romania

6. Academy of Romanian Scientists, Str. Splaiul Independentei no. 54, Sector 5, 050094 Bucharest, Romania

7. Preclinical Department, Apollonia University, Păcurari Street 11, 700511 Iasi, Romania

8. Doctoral School of Geosciences, Faculty of Geography and Geology, Alexandru Ioan Cuza University of Iasi, Bd. Carol I no. 20A, 700505 Iasi, Romania

9. Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Str. Universitatii no. 16, 700115 Iasi, Romania

Abstract

(1) Background: In this study, we aimed to explore the regulatory mechanism of miR-124-3p microglial exosomes, as they were previously reported to modulate neuroinflammation and promote neuronal repair following traumatic brain injury (TBI). (2) Methods: Studies investigating the impact of microglial exosomal miRNAs, specifically miR-124-3p, on injured neurons and brain microvascular endothelial cells (BMVECs) in the context of TBI were reviewed. (3) Results: Animal models of TBI, in vitro cell culture experiments, RNA sequencing analysis, and functional assays were employed to elucidate the mechanisms underlying the effects of miR-124-3p-loaded exosomes on neuroinflammation and neuronal repair. Anti-inflammatory M2 polarization of microglia, mTOR signaling suppression, and BMVECs-mediated autophagy were reported as the main processes contributing to neuroprotection, reduced blood-brain barrier leakage, and improved neurologic outcomes in animal models of TBI. (4) Conclusions: Microglial exosomes, particularly those carrying miR-124-3p, have emerged as promising candidates for therapeutic interventions in TBI. These exosomes exhibit neuroprotective effects, attenuate neuroinflammation, and promote neuronal repair and plasticity. However, further research is required to fully elucidate the underlying mechanisms and optimize their delivery strategies for effective treatment in human TBI cases.

Funder

Romanian Ministry of Research, Innovation, and Digitization, within Program 1—Development of the National RD System, Subprogram 1.2—Institutional Performance—RDI Excellence Funding Projects

Publisher

MDPI AG

Subject

Paleontology,Space and Planetary Science,General Biochemistry, Genetics and Molecular Biology,Ecology, Evolution, Behavior and Systematics

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