Intermittent hypoxia initiated plasticity in humans: A multipronged therapeutic approach to treat sleep apnea and overlapping co-morbidities

Mateika, Jason H.; Komnenov, Dragana

doi:10.1016/j.expneurol.2016.05.011

Cited by 48 publications

(52 citation statements)

References 187 publications

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“…Compared to the NO group, the CIH group showed increased activity of the genioglossus corticomotor area from the 1st to the 14th day. These data indicated that the compensation of genioglossus corticomotor area occurred immediately after CIH and lasted for at least 2 weeks, which was consistent with the report that CIH could initiate respiratory plasticity (6). It is important to understand the mechanism of this compensation because it will be helpful to OSA treatment.…”

Section: Discussionsupporting

confidence: 91%

“…Bradford et al found that episodic hypoxia-evoked persistent increase in genioglossus EMG activity in neonatal rats in vivo (5). A recent study showed that CIH could elicit beneficial outcomes by initiating respiratory plasticity (6). Our previous studies also revealed increased genioglossus corticomotor activity of rats during CIH (7, 8).…”

Section: Introductionmentioning

confidence: 99%

“…Our previous study on rats demonstrated that 5-HT in the raphe nucleus modulated the facilitation of genioglossus corticomotor activity induced by CIH (8). On the other hand, acute intermittent hypoxia-induced hypoglossal long-term facilitation could be blocked by intravenous injection of the α1-adrenergic antagonist, prazosin (PZ) (6, 11). Stettner et al also found that PZ microinjection into the hypoglossal nucleus could cause a greater decrease of hypoglossal nerve activity in rats after the 35th day of hypoxia than those in air (12).…”

Section: Introductionmentioning

confidence: 99%

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Noradrenergic Activation of Hypoglossal Nucleus Modulates the Central Regulation of Genioglossus in Chronic Intermittent Hypoxic Rats

et al. 2017

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Neuromuscular compensation of the genioglossus muscle can be induced by chronic intermittent hypoxia (CIH) in obstructive sleep apnea to maintain upper airway stability. Noradrenergic activation of hypoglossal nucleus plays a critical role in the central control of the genioglossus. However, it remains unknown whether norepinephrine takes part in the central regulation of the genioglossus during CIH. Adult male Wistar rats (n = 32) were studied to explore the influence of noradrenergic activation of hypoglossal nucleus on the central control of the genioglossus at different stages of CIH. The rats were divided into four groups: normal control or normoxic (NO) group, CIH group, CIH + normal saline (NS) group, and CIH + prazosin (PZ, α1-adrenergic antagonist) group. PZ (0.2 mM, 60 nl) and NS (0.9%, 60 nl) were microinjected into the hypoglossal nucleus. The responses of the genioglossus corticomotor area to transcranial magnetic stimulation (TMS) were recorded on the 1st, 7th, 14th, and 21st day of CIH. The CIH group showed significantly shorter TMS latencies on days 1, 7, and 14 (3.85 ± 0.37 vs. 4.58 ± 0.42, 3.93 ± 0.17 vs. 4.49 ± 0.55, 3.79 ± 0.38 vs. 4.39 ± 0.30 ms, P < 0.05), and higher TMS amplitudes on day 1 (2.74 ± 0.87 vs. 1.60 ± 0.52 mV, P < 0.05) of CIH than the NO group. Compared to the CIH + NS group, the CIH + PZ group showed decreased TMS responses (longer latencies and lower amplitudes) only on the 14th day of CIH (3.99 ± 0.28 vs. 4.61 ± 0.48 ms, 2.51 ± 0.67 vs. 1.18 ± 0.62 mV, P < 0.05). These results indicated that noradrenergic activation of the hypoglossal nucleus played a role in the central compensation of genioglossus through α1-adrenoceptor on the 14th day of CIH.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Noradrenergic Activation of Hypoglossal Nucleus Modulates the Central Regulation of Genioglossus in Chronic Intermittent Hypoxic Rats

et al. 2017

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“…More specifically, reductions in therapeutic pressure (El‐Chami et al . , Mateika & Komnenov, ) combined with increases in the arousal threshold could lead to improved treatment compliance and outcome measures (Mateika & Komnenov, ). This effect, combined with the direct beneficial effects of mild forms of intermittent hypoxia that extend beyond motor function to autonomic, cardiovascular, metabolic and neurocognitive function (Mateika et al .…”

Section: Discussionmentioning

confidence: 99%

“…This effect, combined with the direct beneficial effects of mild forms of intermittent hypoxia that extend beyond motor function to autonomic, cardiovascular, metabolic and neurocognitive function (Mateika et al . ; Mateika & Komnenov, ), suggests that multiple beneficial outcomes could transpire when mild intermittent hypoxia is combined with continuous positive airway pressure in treating individuals suffering from respiratory and limb motor disorders.…”

Section: Discussionmentioning

confidence: 99%

Exposure to mild intermittent hypoxia increases loop gain and the arousal threshold in participants with obstructive sleep apnoea

Alex

Panza

Hakim

et al. 2019

The Journal of Physiology

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Key points Repeated daily mild intermittent hypoxia has been endorsed as a therapy to promote the recovery of respiratory and limb motor dysfunction. One possible side‐effect of this therapy is an increase in apnoeic event number and duration, which is particularly relevant to participants with motor disorders coupled with an increased incidence of sleep apnoea. In this study, we report that increases in apnoeic event number and duration, following exposure to daily intermittent hypoxia, are the result of an increase in respiratory loop gain and the arousal threshold, in participants with obstructive sleep apnoea. Daily exposure to mild intermittent hypoxia also led to an increase in the ventilatory response to arousal. Accordingly, individuals with motor disorders receiving mild intermittent hypoxia as a therapy should be screened for the presence of sleep apnoea, and if present, administration of intermittent hypoxia during hours of wakefulness should be combined with continuous positive airway pressure treatment during sleep. Abstract We determined if exposure to mild intermittent hypoxia (MIH) causes an increase in loop gain (LG) and the arousal threshold (AT) during non‐rapid eye movement (NREM) sleep. Male participants with obstructive sleep apnoea (apnoea‐hypopnoea index > 5 events/h), matched for age, body mass index and race were divided into two groups (n = 13 in each group). Following a baseline sleep study, one group was exposed to twelve 4‐min episodes of hypoxia each day for 10 days and the other group to a sham protocol (SP). On Days 1 and 10, a sleep study was completed following exposure to MIH or the SP. For each sleep study, LG and the AT were measured during NREM sleep, using a model‐based approach, and expressed as a fraction of baseline measures. LG increased after exposure to MIH (Day 1: 1.11 ± 0.03, P = 0.002, Day 10: 1.17 ± 0.05, P = 0.001), but not after the SP (Day 1: 1.03 ± 0.04, P = 1.0, Day 10: 1.0 ± 0.02, P = 1.0). AT also increased after exposure to MIH (Day 1: 1.13 ± 0.05, P = 0.01, Day 10: 1.19 ± 0.08, P = 0.05) but not after the SP (Day 1: 1.04 ± 0.05, P = 0.6, Day 10: 0.96 ± 0.04, P = 1.0). Our results might account for increases in apnoea frequency and duration previously observed during NREM sleep following exposure to MIH. Our results also have implications for the use of MIH as a therapeutic modality.

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Effect of lung function on the apnea-hypopnea index in patients with overlap syndrome: a multicenter cross-sectional study

et al. 2019

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Intermittent hypoxia initiated plasticity in humans: A multipronged therapeutic approach to treat sleep apnea and overlapping co-morbidities

Cited by 48 publications

References 187 publications

Noradrenergic Activation of Hypoglossal Nucleus Modulates the Central Regulation of Genioglossus in Chronic Intermittent Hypoxic Rats

Noradrenergic Activation of Hypoglossal Nucleus Modulates the Central Regulation of Genioglossus in Chronic Intermittent Hypoxic Rats

Exposure to mild intermittent hypoxia increases loop gain and the arousal threshold in participants with obstructive sleep apnoea

Effect of lung function on the apnea-hypopnea index in patients with overlap syndrome: a multicenter cross-sectional study

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