Extracellular Vesicle ASC: A Novel Mediator for Lung-Brain Axis in Preterm Brain Injury

Area of Science:

• Neonatal Medicine
• Pulmonology
• Neuroscience

Background:

• Bronchopulmonary dysplasia (BPD) and neurodevelopmental impairment are common in preterm infants.
• The mechanism linking BPD to brain injury remains unclear.
• Extracellular vesicles (EVs) mediate interorgan communication in disease.

Purpose of the Study:

• To investigate the role of alveolar macrophage (AM)-derived EVs in BPD pathogenesis and associated brain injury.
• To assess the impact of high oxygen exposure on EV-ASC content in preterm infants.
• To determine the functional consequences of EV transfer from high-oxygen exposed infants.

Main Methods:

• Assessed AM markers (CD11b, CD11c, CD206) and ASC in plasma EVs from preterm infants.
• Quantified AM-derived EV-ASC in infants on high (HO2) vs. low (LO2) fraction of inspired oxygen.
• Performed adoptive transfer of EVs into newborn mice to assess lung and brain effects.

Main Results:

• Infants on HO2 exhibited increased AM-derived EV-ASC concentrations.
• Adoptive transfer of HO2-EVs into mice induced lung inflammation, impaired alveolarization, and vascular defects characteristic of BPD.
• HO2-EVs crossed the blood-brain barrier, causing hippocampal inflammation, reduced cell survival, and cell death (pyroptosis, necroptosis).

Conclusions:

• AM-derived EV-ASC mediate lung-to-brain cross-talk in BPD pathogenesis.
• This pathway contributes to both lung injury (BPD) and brain injury in preterm infants.
• AM-derived EV-ASC represent potential therapeutic targets for BPD and associated brain damage.