Astrocyte-derived extracellular vesicles inhibit the abnormal activation of immune function in neonatal mice with hypoxic-ischemic brain damage by carrying miR-124-3p

ABSTRACT

Objective

Hypoxic-ischemic brain damage (HIBD) is among the leading causes of neonatal death worldwide. miR-124-3p can be utilized as a potential diagnostic and prognostic biomarker for perinatal asphyxia and HI encephalopathy in newborns. This study investigated the protective effect and mechanism of miR-124-3p in astrocyte-derived extracellular vesicles (ADEVs) in HIBD.

Methods

    The neonatal mouse model of HIBD was established. Astrocytes were transfected with the miR-124-3p inhibitor, followed by isolation and identification of ADEVs (ADEVs + inhi miR). HIBD mice were injected with ADEVs or ADEVs + inhi miR through the lateral ventricle, and neurological function was evaluated based on the modified neurological severity score (mNSS). The infarct volume of mice and the morphological modifications of neurons were observed by TTC staining and hematoxylin-eosin staining. The contents of SOD, GSH-Px, CAT, and MDA in the hippocampus were measured. The neuronal apoptosis, the activation of MPO+ neutrophils, NK cells, and CD3+ cells in CA1 region of the hippocampus was determined by means of TUNEL staining and immunofluorescence.

Results

ADEVs alleviated HIBD in neonatal mice. ADEVs could intrinsically protect mice from HIBD by reducing oxidative stress and apoptosis in hippocampal tissue. ADEVs inhibited the positive expression of MPO+ neutrophils, NK cells, and CD3+ cells in HIBD neonatal mice. ADEVs inhibited the hippocampal immune cells by delivering miR-124-3p in neonatal HIBD mice.

Conclusion

ADEVs can inhibit the abnormal activation of immune function in HIBD by delivering miR-124-3p, thereby eliciting a protective effect on brain damage in neonatal mice.

KEYWORDS:

• HIBD
• Astrocyte
• Extracellular vesicles
• ADEVs
• miR-124-3p
• OS
• Apoptosis
• Immune function

Disclosure statement

No potential conflict of interest was reported by the authors.

Availability of data and material

All the data generated or analyzed during this study are included in this published article.

Author contributions

MCL is the guarantor of integrity of the entire study; MCL contributed to the study concepts, study design, and definition of intellectual content; LCL and MCL contributed to the literature research; LCL and MCL contributed to the manuscript preparation, manuscript editing and review; LCL and MCL contributed to the experimental studies and data acquisition; LCL contributed to the data analysis and statistical analysis. All authors read and approved the final manuscript.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.