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Pathological Consequences of Intermittent Hypoxia in the Central Nervous System

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Abstract

Intermittent hypoxia (IH) is a frequent occurrence in clinical settings. In the last decades, evidence has emerged implicating the gas exchange alterations and sleep disruption associated with those disorders in the high prevalence of cognitive and behavioral deficits afflicting these patients. In an effort to better characterize the role of IH, and to identify potential mechanisms of IH‐induced central nervous system (CNS) dysfunction, a large number of rodent models have been recently developed. The cumulative evidence confirms that IH indeed induces a heterotopic pattern of injury in the brain, particularly affecting cortical, subcortical, and hippocampal regions, ultimately leading to neuronal apoptosis and activation of microglia. These IH‐induced deleterious processes exhibit substantial variability across the lifespan, are under substantial modulatory influences of diet, physical or intellectual activity, and genetic factors, and preferentially recruit oxidative stress and inflammatory pathways. © 2012 American Physiological Society. Compr Physiol 2:1767‐1777, 2012.

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Figure 1. Figure 1.

Schematic representation of the potential interactions between intermittent hypoxia (IH), hypercapnia, and sleep fragmentation associated with sleep breathing disorders and the thus far unknown effect of duration of these processes on either preservation of homeostasis or injury in the CNS. On the left side of the scheme are examples of factors associated with either potentiation or attenuation of the IH‐induced CNS dysfunction. On the right side of the figure are representative components of the thus far elucidated cascade of pro‐oxidative stress or inflammatory pathways that contribute to IH‐associated neuronal injury.



Figure 1.

Schematic representation of the potential interactions between intermittent hypoxia (IH), hypercapnia, and sleep fragmentation associated with sleep breathing disorders and the thus far unknown effect of duration of these processes on either preservation of homeostasis or injury in the CNS. On the left side of the scheme are examples of factors associated with either potentiation or attenuation of the IH‐induced CNS dysfunction. On the right side of the figure are representative components of the thus far elucidated cascade of pro‐oxidative stress or inflammatory pathways that contribute to IH‐associated neuronal injury.

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Shelley X.L. Zhang, Yang Wang, David Gozal. Pathological Consequences of Intermittent Hypoxia in the Central Nervous System. Compr Physiol 2012, 2: 1767-1777. doi: 10.1002/cphy.c100060