Insight from animal models into the cognitive consequences of adult sleep-disordered breathing.
Insight from animal models into the cognitive consequences of adult sleep-disordered breathing.
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从动物模型中洞察成人睡眠呼吸障碍的认知后果。
DOI：
10.1093/ilar.50.3.307
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发表时间：
2009
期刊：
影响因子：
2.5
通讯作者：
Veasey,Sigrid
中科院分区：
文献类型：
--
作者：
Veasey,Sigrid
阻塞性睡眠呼吸暂停（OSA）困扰着数千万美国人和全世界数亿人，因此该疾病可能导致永久性神经损伤的可能性是一个重大问题。许多合并症，包括糖尿病，心血管疾病和肥胖症，与疾病有关，这是相当困难的，如果不是不可能的，在临床研究中，以确定是否增加神经损伤的倾向，或是否单独的OSA导致这样的损伤。尽管如此，很明显，睡眠呼吸暂停中低氧血症的严重程度与认知障碍的严重程度相关，OSA的动物模型有助于阐明这种疾病引起神经行为障碍的可能性，而不依赖于合并症。目前还没有研究重度OSA神经损伤机制的动物模型。由于氧合血红蛋白饱和模式与神经损伤相关，研究人员使用严重睡眠呼吸暂停的氧合模式的啮齿动物模型来研究神经损伤和认知障碍的机制，这些模型为睡眠呼吸暂停氧合模式损伤神经元的分子机制提供了巨大的见解。氧化、炎症和细胞器损伤均导致神经功能障碍。此外，现在已经确定了许多睡眠呼吸暂停损伤的神经元群的损伤分子靶点。研究人员准备利用这些知识开发药物治疗，可能会预防或部分逆转睡眠呼吸暂停引起的神经损伤。
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.