A recent study conducted by researchers from Marshall University and the University of Missouri sheds new light on the role exosomes—small vesicles released by cells—may play in blood-brain barrier (BBB) dysfunction in children with obstructive sleep apnea (OSA), especially those with neurocognitive deficits.
Published in Experimental Neurology earlier this month, the study suggests that exosomes may be a critical factor in the cognitive impairments associated with pediatric OSA. Although the link between OSA and cognitive issues in children has been established, the mechanisms at play have largely remained elusive.
The researchers examined the exosomes in the blood of children with and without OSA-related cognitive deficits and their effects on a 3D BBB model. The study involved 26 children divided into three groups: healthy controls, OSA patients without cognitive deficits, and OSA patients with neurocognitive deficits.
Findings revealed that exosomes from children with both OSA and cognitive impairments disrupted the integrity of the blood-brain barrier. This resulted in reduced trans-endothelial electrical resistance (TEER) and increased permeability. Both OSA groups showed signs of heightened permeability in neurovascular unit cells in monolayer and microfluidic BBB models, indicating a more widespread effect on the barrier’s function.
Further analysis using advanced single-nucleus RNA sequencing (snRNA-seq) uncovered distinct cellular clusters and signaling pathways linked to the different OSA phenotypes, offering deeper insights into the underlying mechanisms of cognitive dysfunction in these children.
“This study significantly advances our understanding of how exosomes linked to OSA can impact the blood-brain barrier, potentially contributing to neurocognitive issues,” said Dr. Abdelnaby Khalyfa, professor at Marshall University Joan C. Edwards School of Medicine and the corresponding author of the study. “By utilizing advanced sequencing methods, we can identify biomarkers and therapeutic targets to better treat children at risk.”
Trupti Joshi, Ph.D., lead author and associate professor at the University of Missouri, emphasized the importance of this research for personalized medicine. “Through cutting-edge data analysis, we have pinpointed biological pathways that play a role in cognitive impairments in children with OSA. This breakthrough could lead to targeted treatments for pediatric patients.”
The study also highlights the collaboration between Marshall University’s clinicians, researchers, and bioinformatics teams, advancing the field of Precision Medicine. Future research will focus on developing point-of-care tests to better identify children at risk for long-term cognitive complications due to OSA.
The co-authors of the study include Dr. Trupti Joshi, Yen On Chan, Ph.D., Zhuanghong Qiao, Ph.D., Leila Kheirandish-Gozal, M.D., M.Sc., all from the University of Missouri, as well as Dr. David Gozal, M.D., M.B.A., Ph.D. (Hon) from Marshall University.
This research emphasizes the importance of exosome analysis in deepening our understanding of pediatric OSA and opens the door to new precision medicine strategies aimed at mitigating cognitive dysfunction in affected children.
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