A new study highlights how exosomes – tiny vesicles released by cells – may play a key role in blood-brain barrier (BBB) dysfunction in children with obstructive sleep apnoea (OSA), particularly those with neurocognitive deficits.
The findings could pave the way for personalized therapeutic strategies for paediatric OSA patients. OSA in children has been linked to cognitive impairments, but the underlying mechanisms remain poorly understood.
This study analysed exosomes in the blood of children with and without OSA-related cognitive deficits and examined their effects on a 3D blood-brain barrier model. Researchers categorised 26 children into three groups: healthy controls, OSA patients without cognitive deficits and OSA patients with neurocognitive deficits.
The study found that exosomes from children with both OSA and neurocognitive deficits disrupted blood-brain barrier (BBB) integrity, leading to reduced trans-endothelial electrical resistance (TEER) and increased permeability.
Additionally, both OSA groups exhibited increased permeability in neurovascular unit cells within monolayer and microfluidic BBB models, suggesting a broader impact on barrier function.
Further analysis using single-nucleus RNA sequencing (snRNA-seq) identified distinct cellular clusters and signalling pathways associated with different OSA phenotypes, providing deeper insight into the mechanisms underlying neurocognitive dysfunction in affected children.
“This research enhances our understanding of how OSA-related exosomes affect the blood-brain barrier, which may contribute to neurocognitive dysfunction,” said Abdelnaby Khalyfa, professor of biomedical sciences at the Marshall University Joan C. Edwards School of Medicine and corresponding author.
“By integrating advanced sequencing techniques, we can identify potential morbidity-related biomarkers and therapeutic targets for children at risk.”
“This successful collaboration between clinicians, researchers at Marshall, and our bioinformatics team is advancing Precision Medicine,” said Trupti Joshi, lead author and associate professor, University of Missouri.
“Using advanced data analysis, our team uncovered key biological pathways linked to cognitive deficits in children with obstructive sleep apnoea. This breakthrough could lead to personalized treatments for paediatric patients.”
The study underscores the importance of in-depth exosome analysis in fostering our understanding paediatric OSA and opens the door for precision medicine approaches to mitigate cognitive complications.
Future research will focus on development of point-of-care testing with the aim to accurately identify those children who suffer from end-morbidity induced by OSA.
