Insight from animal models into the cognitive consequences of adult sleep-disordered breathing.
Obstructive sleep apnea (OSA) afflicts tens of millions of Americans and hundreds of millions of people worldwide, and the possibility that the disease may cause permanent neural injury is therefore a significant concern. Numerous comorbidities--including diabetes, cardiovascular disease, and obesity--are associated with the disease, and it is quite difficult, if not impossible, in clinical studies to determine whether they increase the propensity for neural injury or whether OSA alone causes such injury. It is nonetheless clear that the severity of hypoxemia in sleep apnea correlates with the severity of cognitive impairments, and animal models of OSA have been instrumental in elucidating the potential for this disease to elicit neurobehavioral impairment independent of comorbidities. At present, there is no animal model of severe OSA with which to explore mechanisms of neural injury. Because oxyhemoglobin saturation patterns correlate with neural injury, researchers have used rodent models of the oxygenation patterns of severe sleep apnea to study mechanisms of neural injury and cognitive impairment, and these models have provided tremendous insight into the molecular mechanisms by which sleep apnea oxygenation patterns injure neurons. Oxidative, inflammatory, and organelle injury all contribute to neural dysfunction. Moreover, molecular targets of injury have now been identified for many neuronal groups injured in sleep apnea. Researchers are poised to use this knowledge to develop pharmacotherapies that may prevent or partially reverse neural injury from sleep apnea.
Veasey
Sigrid
S
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. veasey@mail.med.upenn.edu
D000328:Adult; D000818:Animals; D001921:Brain / Q000503:physiopathology; D003072:Cognition Disorders / Q000150:complications* / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology; D051381:Rats; D012893:Sleep Wake Disorders / Q000150:complications* / Q000503:physiopathology; D013552:Swine