Daily acute intermittent hypoxia improves breathing function with acute and chronic spinal injury via distinct mechanisms

Dougherty, Brendan J.; Terada, Jiro; Springborn, Sarah; Vinit, Stéphane; MacFarlane, Peter M.; Mitchell, Gordon S.

doi:10.1016/j.resp.2017.05.004

Cited by 42 publications

(26 citation statements)

References 51 publications

(91 reference statements)

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“…On the other hand, with more chronic spinal injuries (>8 weeks), rAIH‐induced functional recovery switches to a serotonin‐dependent, adenosine‐constrained mechanism (Dougherty et al . ; Navarrete‐Opazo et al . ).…”

Section: Discussionmentioning

confidence: 99%

Phrenic motor neuron adenosine 2A receptors elicit phrenic motor facilitation

Seven

Perim

Hobson

et al. 2018

The Journal of Physiology

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Cervical spinal adenosine 2A (A ) receptor activation elicits a prolonged increase in phrenic nerve activity, an effect known as phrenic motor facilitation (pMF). The specific cervical spinal cells expressing the relevant A receptors for pMF are unknown. This is an important question since the physiological outcome of A receptor activation is highly cell type specific. Thus, we tested the hypothesis that the relevant A receptors for pMF are expressed in phrenic motor neurons per se versus non-phrenic neurons of the cervical spinal cord. A receptor immunostaining significantly colocalized with NeuN-positive neurons (89 ± 2%). Intrapleural siRNA injections were used to selectively knock down A receptors in cholera toxin B-subunit-labelled phrenic motor neurons. A receptor knock-down was verified by a ∼45% decrease in A receptor immunoreactivity within phrenic motor neurons versus non-targeting siRNAs (siNT; P < 0.05). There was no evidence for knock-down in cervical non-phrenic motor neurons. In rats that were anaesthetized, subjected to neuromuscular blockade and ventilated, pMF induced by cervical (C3-4) intrathecal injections of the A receptor agonist CGS21680 was greatly attenuated in siA (21%) versus siNT treated rats (147%; P < 0.01). There were no significant effects of siA on phrenic burst frequency. Collectively, our results support the hypothesis that phrenic motor neurons express the A receptors relevant to A receptor-induced pMF.

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Section: Discussionmentioning

confidence: 99%

Phrenic motor neuron adenosine 2A receptors elicit phrenic motor facilitation

Seven

Perim

Hobson

et al. 2018

The Journal of Physiology

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“…Opportunities for further investigation include interventions that promote ventilatory recovery or long-term facilitation, [48][49][50] such as the use of daily administration of intermittent hypoxia or pharmacologic agents, which capitalizes on the intrinsic plasticity of the respiratory system to enhance ventilatory motor output and restore respiratory function via serotonin and brain derivative neutrophilic factor-dependent mechanisms. 51,52 Conclusions SDB is common among individuals with SCI/D, particularly among those with cervical injuries. The mechanism(s) for the increased prevalence of SDB after surviving SCI are not clear yet, but evidence points toward complex pathways that include hypoventilation, upper airway collapsibility, and neuromuscular weakness.…”

Section: Future Directionsmentioning

confidence: 96%

Sleep-Disordered Breathing and Spinal Cord Injury

Sankari

Vaughan

Bascom

et al. 2019

Chest

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Individuals living with spinal cord injury or disease (SCI/D) are at increased risk for sleep-disordered breathing (SDB), with a prevalence that is three-to fourfold higher than the general population. The main features of SDB, including intermittent hypoxemia and sleep fragmentation, have been linked to adverse cardiovascular outcomes including nocturnal hypertension in patients with SCI/D. The relationship between SDB and SCI/D may be multifactorial in nature given that level and completeness of injury can affect central control of respiration and upper airway collapsibility differently, promoting central and/or obstructive types of SDB. Despite the strong association between SDB and SCI/D, access to diagnosis and management remains limited. This review explores the role of SCI/D in the pathogenesis of SDB, poor sleep quality, the barriers in diagnosing and managing SDB in SCI/D, and the alternative approaches and future directions in the treatment of SDB, such as novel pharmacologic and nonpharmacologic treatments.

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“…Complete or incomplete spinal cord injuries are characterized by spared synaptic pathways below the level of the injury. Intermittent hypoxia elicits plasticity in the spinal cord and strengthens these spared synaptic pathways, expressed as respiratory and somatic functional recovery in both experimental animals and humans with traumatic spinal cord injury (Navarrete-Opazo et al, 2015 , 2017a , b ; Dougherty et al, 2017 ; Trumbower et al, 2017 ). Table 5 lists studies reporting beneficial neurological impact after a wide range of intermittent hypoxia exposure protocols.…”

Section: Biological Effects Of Intermittent Hypoxia Exposurementioning

confidence: 99%

Physiological and Biological Responses to Short-Term Intermittent Hypobaric Hypoxia Exposure: From Sports and Mountain Medicine to New Biomedical Applications

et al. 2018

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In recent years, the altitude acclimatization responses elicited by short-term intermittent exposure to hypoxia have been subject to renewed attention. The main goal of short-term intermittent hypobaric hypoxia exposure programs was originally to improve the aerobic capacity of athletes or to accelerate the altitude acclimatization response in alpinists, since such programs induce an increase in erythrocyte mass. Several model programs of intermittent exposure to hypoxia have presented efficiency with respect to this goal, without any of the inconveniences or negative consequences associated with permanent stays at moderate or high altitudes. Artificial intermittent exposure to normobaric hypoxia systems have seen a rapid rise in popularity among recreational and professional athletes, not only due to their unbeatable cost/efficiency ratio, but also because they help prevent common inconveniences associated with high-altitude stays such as social isolation, nutritional limitations, and other minor health and comfort-related annoyances. Today, intermittent exposure to hypobaric hypoxia is known to elicit other physiological response types in several organs and body systems. These responses range from alterations in the ventilatory pattern to modulation of the mitochondrial function. The central role played by hypoxia-inducible factor (HIF) in activating a signaling molecular cascade after hypoxia exposure is well known. Among these targets, several growth factors that upregulate the capillary bed by inducing angiogenesis and promoting oxidative metabolism merit special attention. Applying intermittent hypobaric hypoxia to promote the action of some molecules, such as angiogenic factors, could improve repair and recovery in many tissue types. This article uses a comprehensive approach to examine data obtained in recent years. We consider evidence collected from different tissues, including myocardial capillarization, skeletal muscle fiber types and fiber size changes induced by intermittent hypoxia exposure, and discuss the evidence that points to beneficial interventions in applied fields such as sport science. Short-term intermittent hypoxia may not only be useful for healthy people, but could also be considered a promising tool to be applied, with due caution, to some pathophysiological states.

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Daily acute intermittent hypoxia improves breathing function with acute and chronic spinal injury via distinct mechanisms

Cited by 42 publications

References 51 publications

Phrenic motor neuron adenosine 2A receptors elicit phrenic motor facilitation

Phrenic motor neuron adenosine 2A receptors elicit phrenic motor facilitation

Sleep-Disordered Breathing and Spinal Cord Injury

Physiological and Biological Responses to Short-Term Intermittent Hypobaric Hypoxia Exposure: From Sports and Mountain Medicine to New Biomedical Applications

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