Two-week normobaric intermittent-hypoxic exposures stabilize cerebral perfusion during hypocapnia and hypercapnia

Zhang, Peizhen; Shi, Xiangrong; Downey, H. Fred

doi:10.1177/1535370214562339

Cited by 15 publications

(13 citation statements)

References 44 publications

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“…Moderate IH in early life can accelerate brain development and improve learning abilities (Zhang, Chen, Du, Chen, & Zhu, ), which is related to increased neurogenesis and synaptic plasticity. In IH preconditioning of cerebral ischemia and other diseases, preconditioning attenuates the ischemic response and effectively downregulates metabolic pathways of ischemia‐induced immune responses (Goryacheva et al, ; Mashina et al, ; Zhang, Shi, & Downey, ). Similar to cerebral ischemia, AD also presents with inflammation, decreased synapse formation, and cognitive impairment.…”

Section: Discussionmentioning

confidence: 99%

Intermittent hypoxia improves cognition and reduces anxiety‐related behavior in APP/PS1 mice

Meng

Wang

2019

Brain and Behavior

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Introduction:Although hypoxia can exacerbate symptoms of various neurological disorders, accumulating evidence has indicated that intermittent hypoxia (IH) may exert protective effects against brain diseases. In the present study, we aimed to determine whether exposure to IH exerts beneficial effects in a transgenic murine model of Alzheimer's disease (AD). Because comorbid anxiety is prevalent among patients with AD, we explored the effects of IH on anxiety-like behaviors and associated factors in APP/PS1 mice.Methods: APP/PS1 mice were subjected to IH for two weeks. We assessed cognitive performance and anxiety-related behavior using standard behavioral assessments.Amyloid beta (Aβ) levels in the hippocampus were assessed using immunofluorescence and enzyme-linked immunosorbent assays (ELISA). We also assessed cell morphology and brain-derived neurotrophic factor (BDNF) expression in the hippocampus.Results: Exposure to IH significantly increased cognitive performance and decreased anxiety-related behaviors in APP/PS1 mice. Immunofluorescence and ELISA results revealed that IH pretreatment significantly lowered Aβ levels in the cortex and hippocampus. Morphological studies validated the neuroprotective effect of IH exposure on hippocampal neurogenesis. Molecular studies revealed IH-enhanced BDNF expression and inhibition of apoptosis-related protein expression in the hippocampus of APP/PS1 mice. Conclusions:Our study demonstrates that IH improves cognition and reduces anxiety in a murine model of AD. Thus, further studies are required to determine whether IH can be used as a preventive/adjuvant therapy in patients with AD.

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Section: Discussionmentioning

confidence: 99%

Intermittent hypoxia improves cognition and reduces anxiety‐related behavior in APP/PS1 mice

Meng

Wang

2019

Brain and Behavior

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“…15,16 In contrast, therapeutic IHT utilizes exposures to moderately severe hypoxia produced in hypobaric chambers or by inspiring normobaric atmospheres with O 2 content lowered to approximately 10%. Typical normobaric IHT protocols utilized in our laboratories for human [93][94][95] and animal 96-100 research involve 5-8 cycles/ day of inspiration of 10% O 2 for 5-10 min, with intervening 4 min normoxia (21% O 2 ), over the course of 14-20 consecutive days. Rats and dogs subjected to these protocols showed no distress, and humans (including coauthor HFD) reported no discomfort.…”

Section: Intermittent Hypoxic Training (Iht) Improves Cerebrovascularmentioning

confidence: 99%

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

Манухина

Downey

Shi

et al. 2016

Exp Biol Med (Maywood)

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Alzheimer's disease (AD) is a leading cause of death and disability among older adults. Modifiable vascular risk factors for AD (VRF) include obesity, hypertension, type 2 diabetes mellitus, sleep apnea, and metabolic syndrome. Here, interactions between cerebrovascular function and development of AD are reviewed, as are interventions to improve cerebral blood flow and reduce VRF. Atherosclerosis and small vessel cerebral disease impair metabolic regulation of cerebral blood flow and, along with microvascular rarefaction and altered trans-capillary exchange, create conditions favoring AD development. Although currently there are no definitive therapies for treatment or prevention of AD, reduction of VRFs lowers the risk for cognitive decline. There is increasing evidence that brief repeated exposures to moderate hypoxia, i.e. intermittent hypoxic training (IHT), improve cerebral vascular function and reduce VRFs including systemic hypertension, cardiac arrhythmias, and mental stress. In experimental AD, IHT nearly prevented endothelial dysfunction of both cerebral and extra-cerebral blood vessels, rarefaction of the brain vascular network, and the loss of neurons in the brain cortex. Associated with these vasoprotective effects, IHT improved memory and lessened AD pathology. IHT increases endothelial production of nitric oxide (NO), thereby increasing regional cerebral blood flow and augmenting the vaso-and neuroprotective effects of endothelial NO. On the other hand, in AD excessive production of NO in microglia, astrocytes, and cortical neurons generates neurotoxic peroxynitrite. IHT enhances storage of excessive NO in the form of S-nitrosothiols and dinitrosyl iron complexes. Oxidative stress plays a pivotal role in the pathogenesis of AD, and IHT reduces oxidative stress in a number of experimental pathologies. Beneficial effects of IHT in experimental neuropathologies other than AD, including dyscirculatory encephalopathy, ischemic stroke injury, audiogenic epilepsy, spinal cord injury, and alcohol withdrawal stress have also been reported. Further research on the potential benefits of IHT in AD and other brain pathologies is warranted.

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“…Hence, a longer duration of IH exposure appears to be necessary to alter the cerebrovascular response to hypoxia. Finally, IH does not appear to impact the CBF response to hypercapnia in healthy humans, with recent studies reporting no change after 10 (Querido et al 2015) and 14 days of IH (Zhang et al 2015). However, the IH protocol used in these two studies (Table 1) is very different from that induced by OSA.…”

Section: Detrimental Effects Of Intermittent Hypoxiamentioning

confidence: 79%

“…In the only animal study, exposure to 14 days (12 h day −1 ) of IH A. E. Beaudin and others (ODI = 15) abolished the ability of the middle cerebral artery to dilate in response to an acute hypoxic challenge (Phillips et al 2004). Finally, IH does not appear to impact the CBF response to hypercapnia in healthy humans, with recent studies reporting no change after 10 (Querido et al 2015) and 14 days of IH (Zhang et al 2015). 5 min isocapnic hypoxia and 5 min of room air for 1 h day −1 ) and to 4 days of IH simulating an ODI of 15 (Foster et al 2005(Foster et al , 2009aQuerido et al 2015).…”

Section: Detrimental Effects Of Intermittent Hypoxiamentioning

confidence: 79%

Impact of obstructive sleep apnoea and intermittent hypoxia on cardiovascular and cerebrovascular regulation

Beaudin

Waltz

Hanly

et al. 2017

Experimental Physiology

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What is the topic of this review? This review examines the notion that obstructive sleep apnoea (OSA) and intermittent hypoxia (IH) have hormetic effects on vascular health. What advances does it highlight? Clinical (OSA patient) and experimental animal and human models report that IH is detrimental to vascular regulation. However, mild IH and, by extension, mild OSA also have physiological and clinical benefits. This review highlights clinical and experimental animal and human data linking OSA and IH to vascular disease and discusses how hormetic effects of OSA and IH relate to OSA severity, IH intensity and duration, and patient/subject age. Obstructive sleep apnoea (OSA) is associated with increased risk of cardiovascular and cerebrovascular disease, a consequence attributed in part to chronic intermittent hypoxia (IH) resulting from repetitive apnoeas during sleep. Although findings from experimental animal, and human, models have shown that IH is detrimental to vascular regulation, the severity of IH used in many of these animal studies [e.g. inspired fraction of oxygen (FI,O2) = 2-3%; oxygen desaturation index = 120 events h ] is considerably greater than that observed in the majority of patients with OSA. This may also explain disparities between animal and recently developed human models of IH, where IH severity is, by necessity, less severe (e.g. FI,O2 = 10-12%; oxygen desaturation index = 15-30 events h ). In this review, we highlight the current knowledge regarding the impact of OSA and IH on cardiovascular and cerebrovascular regulation. In addition, we critically discuss the recent notion that OSA and IH may have hormetic effects on vascular health depending on conditions such as OSA severity, IH intensity and duration, and age. In general, data support an independent causal link between OSA and vascular disease, particularly for patients with severe OSA. However, the data are equivocal for older OSA patients and patients with mild OSA, because advanced age and short-duration, low-intensity IH have been reported to provide a degree of protection against IH and ischaemic events such as myocardial infarction and stroke, respectively. Overall, additional studies are needed to investigate the beneficial/detrimental effects of mild OSA on the various vascular beds.

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Two-week normobaric intermittent-hypoxic exposures stabilize cerebral perfusion during hypocapnia and hypercapnia

Cited by 15 publications

References 44 publications

Intermittent hypoxia improves cognition and reduces anxiety‐related behavior in APP/PS1 mice

Intermittent hypoxia improves cognition and reduces anxiety‐related behavior in APP/PS1 mice

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

Impact of obstructive sleep apnoea and intermittent hypoxia on cardiovascular and cerebrovascular regulation

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