Acute intermittent hypercapnic hypoxia and cerebral neurovascular coupling in males and females

Vermeulen, Tyler D.; Benbaruj, Jenna; Brown, Courtney V.; Shafer, Brooke M.; Floras, John S.; Foster, Glen E.

doi:10.1016/j.expneurol.2020.113441

Cited by 9 publications

(3 citation statements)

References 48 publications

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“…It is worth noting that this type of mask-setting has been also applied to investigate the effects of intermittent hypercapnia (realistic cycles of 30 s of hypercapnic hypoxia followed by 2 min of air, i.e., 24 events/h)) in healthy humans [163]. Interestingly, this human model has recently been used to investigate whether the effects of intermittent hypoxia/hypercapnia are different in men and women [164,165]. A second possible procedure for applying IH to humans is different only from a practical perspective.…”

Section: Experimental Sa Models In Healthy Volunteersmentioning

confidence: 99%

Experimental Models to Study End-Organ Morbidity in Sleep Apnea: Lessons Learned and Future Directions

Farré

Almendros

Martínez-García

et al. 2022

IJMS

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Sleep apnea (SA) is a very prevalent sleep breathing disorder mainly characterized by intermittent hypoxemia and sleep fragmentation, with ensuing systemic inflammation, oxidative stress, and immune deregulation. These perturbations promote the risk of end-organ morbidity, such that SA patients are at increased risk of cardiovascular, neurocognitive, metabolic and malignant disorders. Investigating the potential mechanisms underlying SA-induced end-organ dysfunction requires the use of comprehensive experimental models at the cell, animal and human levels. This review is primarily focused on the experimental models employed to date in the study of the consequences of SA and tackles 3 different approaches. First, cell culture systems whereby controlled patterns of intermittent hypoxia cycling fast enough to mimic the rates of episodic hypoxemia experienced by patients with SA. Second, animal models consisting of implementing realistic upper airway obstruction patterns, intermittent hypoxia, or sleep fragmentation such as to reproduce the noxious events characterizing SA. Finally, human SA models, which consist either in subjecting healthy volunteers to intermittent hypoxia or sleep fragmentation, or alternatively applying oxygen supplementation or temporary nasal pressure therapy withdrawal to SA patients. The advantages, limitations, and potential improvements of these models along with some of their pertinent findings are reviewed.

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Section: Experimental Sa Models In Healthy Volunteersmentioning

confidence: 99%

Experimental Models to Study End-Organ Morbidity in Sleep Apnea: Lessons Learned and Future Directions

Farré

Almendros

Martínez-García

et al. 2022

IJMS

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show abstract

“…In a published companion article, we reported that intermittent exposure to concurrent hypoxia and hypercapnia (AIHH: acute intermittent hypercapnic-hypoxia; ∼9.5% inspired O 2 ; ∼4.5% inspired CO 2 ) elicited robust facilitation of diaphragm motor-evoked potential (MEP) reflection volitional pathways to phrenic motor neurons, and mouth occlusion pressure in 100 ms (P0.1), reflecting automatic ventilatory control, in healthy adults. 3 Combined hypoxia and hypercapnia are more effective at triggering respiratory motor plasticity in humans, 4 , 5 possibly because greater carotid chemoreceptor activation augments serotonergic raphe neuron activity more than hypoxia alone, 6 , 7 and/or direct activation of raphe neurons by hypercapnia, 8 thereby enhancing cell signaling cascades that strengthen synapses onto phrenic motor neurons. Consistent with published human AIH trials, 2 ∼40% of participants respond minimally to AIHH (defined as <25% increase in diaphragm MEP amplitudes).…”

Section: Introductionmentioning

confidence: 99%

APOE4, Age, and Sex Regulate Respiratory Plasticity Elicited by Acute Intermittent Hypercapnic-Hypoxia

et al. 2023

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Rationale Acute intermittent hypoxia (AIH) is a promising strategy to induce functional motor recovery following chronic spinal cord injuries and neurodegenerative diseases. Although significant results are obtained, human AIH trials report considerable inter-individual response variability. Objectives Identify individual factors (e.g., genetics, age, and sex) that determine response magnitude of healthy adults to an optimized AIH protocol, acute intermittent hypercapnic-hypoxia (AIHH). Methods Associations of individual factors with the magnitude of AIHH (15, 1-min O2 = 9.5%, CO2 = 5% episodes) induced changes in diaphragm motor-evoked potential amplitude (MEP) and inspiratory mouth occlusion pressures (P0.1) were evaluated in 17 healthy individuals (age = 27 ± 5 years) compared to Sham. Single nucleotide polymorphisms (SNPs) in genes linked with mechanisms of AIH induced phrenic motor plasticity (BDNF, HTR2A, TPH2, MAOA, NTRK2) and neuronal plasticity (apolipoprotein E, APOE) were tested. Variations in AIHH induced plasticity with age and sex were also analyzed. Additional experiments in humanized (h)ApoE knock-in rats were performed to test causality. Results AIHH-induced changes in diaphragm MEP amplitudes were lower in individuals heterozygous for APOE4 (i.e., APOE3/4) allele versus other APOE genotypes (p = 0.048). No significant differences were observed between any other SNPs investigated, notably BDNFval/met (all p > 0.05). Males exhibited a greater diaphragm MEP enhancement versus females, regardless of age (p = 0.004). Age was inversely related with change in P0.1 within the limited age range studied (p = 0.007). In hhApoE4 knock-in rats, AIHH-induced phrenic motor plasticity was significantly lower than hApoE3 controls (p < 0.05). Conclusions APOE4 genotype, sex and age are important biological determinants of AIHH-induced respiratory motor plasticity in healthy adults.

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“…In a published companion article, we reported that intermittent exposure to concurrent hypoxia and hypercapnia (AIHH: acute intermittent hypercapnic-hypoxia; ~9.5% inspired O 2 ; ~4.5% inspired CO 2 ) elicited robust facilitation of diaphragm motor-evoked potential, MEP, reflection volitional pathways to phrenic motor neurons, and mouth occlusion pressure in 100 msec (P 0.1 ), reflecting automatic ventilatory control, in healthy adults [3]. Combined hypoxia and hypercapnia are more effective at triggering respiratory motor plasticity in humans [4, 5], possibly because greater carotid chemoreceptor activation augments serotonergic raphe neuron activity more than hypoxia alone [6, 7], and/or direct activation of raphe neurons by hypercapnia [8], thereby enhancing cell signaling cascades that strengthen synapses onto phrenic motor neurons. Consistent with published human AIH trials [2], ~40% of participants respond minimally to AIHH (defined as <25% increase in diaphragm MEP amplitudes).…”

Section: Introductionmentioning

confidence: 99%

APOE4, Age & Sex Regulate Respiratory Plasticity Elicited By Acute Intermittent Hypercapnic-Hypoxia

Nair

Welch

Marciante

et al. 2023

Preprint

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Rationale: Acute intermittent hypoxia (AIH) is a promising strategy to induce functional motor recovery following chronic spinal cord injuries and neurodegenerative diseases. Although significant results are obtained, human AIH trials report considerable inter-individual response variability. Objectives: Identify individual factors (e.g., genetics, age, and sex) that determine response magnitude of healthy adults to an optimized AIH protocol, acute intermittent hypercapnic-hypoxia (AIHH). Methods: Associations of individual factors with the magnitude of AIHH (15, 1-min O2=9.5%, CO2=5% episodes) induced changes in diaphragm motor-evoked potential amplitude (MEP) and inspiratory mouth occlusion pressures (P0.1) were evaluated in 17 healthy individuals (age=27±5 years) compared to Sham. Single nucleotide polymorphisms (SNPs) in genes linked with mechanisms of AIH induced phrenic motor plasticity (BDNF, HTR2A, TPH2, MAOA, NTRK2) and neuronal plasticity (apolipoprotein E, APOE) were tested. Variations in AIHH induced plasticity with age and sex were also analyzed. Additional experiments in humanized (h)ApoE knock-in rats were performed to test causality. Results: AIHH-induced changes in diaphragm MEP amplitudes were lower in individuals heterozygous for APOE4 (i.e., APOE3/4) allele versus other APOE genotypes (p=0.048). No significant differences were observed between any other SNPs investigated, notably BDNFval/met (all p>0.05). Males exhibited a greater diaphragm MEP enhancement versus females, regardless of age (p=0.004). Age was inversely related with change in P0.1 within the limited age range studied (p=0.007). In hApoE4 knock-in rats, AIHH-induced phrenic motor plasticity was significantly lower than hApoE3 controls (p<0.05). Conclusions: APOE4 genotype, sex and age are important biological determinants of AIHH-induced respiratory motor plasticity in healthy adults.

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Acute intermittent hypercapnic hypoxia and cerebral neurovascular coupling in males and females

Cited by 9 publications

References 48 publications

Experimental Models to Study End-Organ Morbidity in Sleep Apnea: Lessons Learned and Future Directions

Experimental Models to Study End-Organ Morbidity in Sleep Apnea: Lessons Learned and Future Directions

APOE4, Age, and Sex Regulate Respiratory Plasticity Elicited by Acute Intermittent Hypercapnic-Hypoxia

APOE4, Age & Sex Regulate Respiratory Plasticity Elicited By Acute Intermittent Hypercapnic-Hypoxia

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