Exosomes, blood–brain barrier, and cognitive dysfunction in pediatric sleep apnea

Abstract

Obstructive sleep apnea is a relatively prevalent condition in children, usually related to enlarged upper airway lymphadenoid tissues, and further aggravated by concurrent obesity. Similar to adults, children with sleep-disordered breathing (SDB) are at increased risk for developing end-organ morbidities usually encompassing cardiometabolic and neurobehavioral and cognitive functions. Although the probability of such end-organ morbidities increases with the severity of SDB, the proportion of unaffected children is still high in very severe cases, thereby prompting exploration of the mechanism underlying such divergent phenotypes as potential biomarkers or therapeutic targets. In this context, we here describe a hypothetical framework, whereby SDB leads to release of circulating exosomes, and their cargo will differ in patients with and without neurocognitive deficits. Furthermore, we propose that exosomes of patients with SDB and measurable neurocognitive alterations will readily disrupt the blood brain barrier (BBB). Such BBB disruption then mediates the cascade of pathophysiological events in vulnerable brain regions within the CNS, ultimately leading to gray matter losses and disrupted neural networks in regions underlying typically affected functions such as attention, executive, and memory. Thus, exosomal cargo may not only provide biomarker indicators of neurocognitive risk in children suffering from SDB, but also guide putative therapeutic targets aimed at preventing or palliating such important morbidity.