Circulating exosomes in pediatric obstructive sleep apnea with or without neurocognitive deficits and their effects...

Area of Science:

• Neuroscience
• Cell Biology
• Pediatrics

Background:

• Obstructive sleep apnea (OSA) in children is associated with cognitive impairments.
• Blood-brain barrier (BBB) dysfunction is a potential mechanism linking OSA to neurocognitive deficits.
• Exosomes, released by cells, carry molecular cargo reflecting cellular states.

Purpose of the Study:

• To investigate the impact of exosomes from children with OSA, with or without cognitive deficits, on neurovascular unit (NVU) models.
• To assess how these exosomes affect BBB integrity, permeability, and angiogenesis.
• To identify intercellular signaling pathways involved using single-nucleus RNA sequencing (snRNA-seq).

Main Methods:

• Plasma exosomes were isolated from three groups of children: healthy controls, OSA without cognitive deficits (OSA-NG), and OSA with neurocognitive deficits (OSA-POS).
• Exosomes were applied to human 3D NVU spheroids and monolayer/microfluidic BBB models.
• Barrier integrity (TEER, ZO1 staining), permeability, and angiogenesis (tube formation) were measured.
• snRNA-seq and CellChat analysis were performed to identify signaling pathways.

Main Results:

• Exosomes from OSA-POS children significantly disrupted BBB integrity (reduced TEER, impaired ZO1 staining) in 3D NVU spheroids.
• Both OSA-POS and OSA-NG exosomes increased BBB permeability in NVU cell models.
• snRNA-seq revealed distinct cell clusters and intercellular communication pathways specific to the OSA groups.

Conclusions:

• Exosomes from children with OSA, particularly those with cognitive deficits, can impair BBB function.
• The 3D NVU spheroid model is effective for studying exosome effects on the BBB.
• Integrating exosome analysis with snRNA-seq can elucidate mechanisms of neurocognitive dysfunction in pediatric OSA, aiding personalized treatment strategies.