HUNTINGTON, W.Va. – A new study by researchers from Marshall University and the University of Missouri highlights how exosomes—tiny vesicles released by cells—may play a key role in blood-brain barrier (BBB) dysfunction in children with obstructive sleep apnea (OSA), particularly those with neurocognitive deficits.
The findings, published online earlier this month in Experimental Neurology , could pave the way for personalized therapeutic strategies for pediatric OSA patients. OSA in children has been linked to cognitive impairments, but the underlying mechanisms remain poorly understood. This study analyzed 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 categorized 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 signaling 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, M.S., Ph.D. , professor of biomedical sciences at the Marshall University Joan C. Edwards School of Medicine and the corresponding author on the study. “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, PhD , lead author and associate professor, University of Missouri Department of Biomedical Informatics, Biostatistics and Medical Epidemiology. “Using advanced data analysis, our team uncovered key biological pathways linked to cognitive deficits in children with obstructive sleep apnea. This breakthrough could lead to personalized treatments for pediatric patients."
In addition to Khalyfa, co-authors on the study include Trupti Joshi, Ph.D., Yen On Chan, Ph.D., Zhuanghong Qiao, Ph.D., and Leila Kheirandish-Gozal, M.D., M.Sc., all of the University of Missouri, and David Gozal, M.D., M.B.A., Ph.D. (Hon) of Marshall University. Funding for the study was supported by startup funds to Dr. Khalyfa at Marshall University.
The study underscores the importance of in-depth exosome analysis in fostering our understanding pediatric 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,
To read the article in its entirety, please visit https://doi.org/10.1016/j.expneurol.2025.115188 .
Experimental Neurology
10.1016/j.expneurol.2025.115188
Randomized controlled/clinical trial
Human tissue samples
Circulating exosomes in pediatric obstructive sleep apnea with or without neurocognitive deficits and their effects on a 3D-blood-brain barrier spheroid model
21-Mar-2025