Adaptation to intermittent hypoxia restricts nitric oxide overproduction and prevents beta-amyloid toxicity in rat brain

Goryacheva, Anna V.; Kruglov, S. V.; Pshennikova, M. G.; Smirin, Boris V.; Malyshev, I. Yu.; Барсков, И. В.; Viktorov, I. V.; Downey, H. Fred; Манухина, Е. Б.

doi:10.1016/j.niox.2010.08.005

Cited by 31 publications

(29 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, although adaptation to hypoxia per se moderately increases NO production, 112,131 it prevents cytotoxic NO overproduction in experimental AD and alleviates adverse effects of AD on memory. 143 NO can be bound into S-nitrosothiols and dinitrosyl iron complexes for transport and intracellular storage. [147][148][149] These NO stores are formed with any increase in NO, so by sequestering excess free NO, these stores can provide protection by buffering NO overproduction.…”

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)

View full text Add to dashboard Cite

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.

show abstract

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)

View full text Add to dashboard Cite

show abstract

“…The authors declare that there are no conflicts of interest Uncited references Q2 (Goryacheva et al, 2010;Sharma et al, 2013).…”

Section: Conflict Of Interestmentioning

confidence: 99%

Mitochondrial function in rat cerebral cortex and hippocampus after short- and long-term hypobaric hypoxia

et al. 2015

View full text Add to dashboard Cite

“…In a rat model of Alzheimer's, 2 weeks of 4 hr daily exposures to hypobaric hypoxia reduced the impairment of memory retention and loss of cortical neurons after intracerebral injections of beta-amyloid. 43 Intermittent hypoxia (2 weeks of 15 hr daily exposures to hypobaric hypoxia) was also found to be protective in rats following L-buthionine-[S,R]-sulfoximine (L-BSO) infusion, a model of Parkinson's which impairs striatal dopaminergic transmission. 44 However, these models of Alzheimer's and Parkinson's only investigated the short-term effects of hypoxic preconditioning.…”

Section: Discussionmentioning

confidence: 99%

“…44 However, these models of Alzheimer's and Parkinson's only investigated the short-term effects of hypoxic preconditioning. 43,44 Investigating the long-term neuroprotection induced by RHP may be a fruitful future direction for research. Furthermore, the neuroprotection induced by RHP may extend to improved BBB integrity in mouse models of Alzheimer's, which could be analyzed with the EB.…”

Section: Discussionmentioning

confidence: 99%

Quantification of Neurovascular Protection Following Repetitive Hypoxic Preconditioning and Transient Middle Cerebral Artery Occlusion in Mice

Poinsatte¹,

Selvaraj²,

Ortega³

et al. 2015

JoVE

View full text Add to dashboard Cite

Experimental animal models of stroke are invaluable tools for understanding stroke pathology and developing more effective treatment strategies. A 2 week protocol for repetitive hypoxic preconditioning (RHP) induces long-term protection against central nervous system (CNS) injury in a mouse model of focal ischemic stroke. RHP consists of 9 stochastic exposures to hypoxia that vary in both duration (2 or 4 hr) and intensity (8% and 11% O 2 ). RHP reduces infarct volumes, blood-brain barrier (BBB) disruption, and the post-stroke inflammatory response for weeks following the last exposure to hypoxia, suggesting a long-term induction of an endogenous CNS-protective phenotype. The methodology for the dual quantification of infarct volume and BBB disruption is effective in assessing neurovascular protection in mice with RHP or other putative neuroprotectants. Adult male Swiss Webster mice were preconditioned by RHP or duration-equivalent exposures to 21% O 2 (i.e. room air). A 60 min transient middle cerebral artery occlusion (tMCAo) was induced 2 weeks following the last hypoxic exposure. Both the occlusion and reperfusion were confirmed by transcranial laser Doppler flowmetry. Twenty-two hr after reperfusion, Evans Blue (EB) was intravenously administered through a tail vein injection. 2 hr later, animals were sacrificed by isoflurane overdose and brain sections were stained with 2,3,5-triphenyltetrazolium chloride (TTC). Infarcts volumes were then quantified. Next, EB was extracted from the tissue over 48 hr to determine BBB disruption after tMCAo. In summary, RHP is a simple protocol that can be replicated, with minimal cost, to induce long-term endogenous neurovascular protection from stroke injury in mice, with the translational potential for other CNS-based and systemic pro-inflammatory disease states. Video LinkThe video component of this article can be found at

show abstract

Adaptation to intermittent hypoxia restricts nitric oxide overproduction and prevents beta-amyloid toxicity in rat brain

Cited by 31 publications

References 57 publications

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

Mitochondrial function in rat cerebral cortex and hippocampus after short- and long-term hypobaric hypoxia

Quantification of Neurovascular Protection Following Repetitive Hypoxic Preconditioning and Transient Middle Cerebral Artery Occlusion in Mice

Contact Info

Product

Resources

About