Acute intermittent hypoxia and respiratory muscle recruitment in people with amyotrophic lateral sclerosis: A preliminary study

Sajjadi, Elaheh; Seven, Yasin B.; Ehrbar, Jessica; Wymer, James P.; Mitchell, Gordon S.; Smith, Barbara K.

doi:10.1016/j.expneurol.2021.113890

Cited by 22 publications

(13 citation statements)

References 86 publications

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“…In the first study in tAIH in people with ALS, Sajjadi and colleagues 135 examined tAIH effects on collective respiratory muscle activity and breathing. The authors demonstrated that, when compared to a session where subjects were administered sham tAIH, a single tAIH session enhanced tidal volume, minute ventilation and collective respiratory muscle activity during quiet breathing 1 h after the session was completed.…”

Section: Therapeutic Acute Intermittent Hypoxia (Taih)mentioning

confidence: 99%

Respiratory therapies for Amyotrophic Lateral Sclerosis: A state of the art review

et al. 2023

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition noteworthy for upper and lower motor neuron death. Involvement of respiratory motor neuron pools leads to progressive pathology. These impairments include decreases in neural activation and muscle coordination, progressive airway obstruction, weakened airway defenses, restrictive lung disease, increased risk of pulmonary infections, and weakness and atrophy of respiratory muscles. These neural, airway, pulmonary, and neuromuscular changes deteriorate integrated respiratory-related functions including sleep, cough, swallowing, and breathing. Ultimately, respiratory complications account for a large portion of morbidity and mortality in ALS. This state-of-the-art review highlights applications of respiratory therapies for ALS, including lung volume recruitment, mechanical insufflation-exsufflation, non-invasive ventilation, and respiratory strength training. Therapeutic acute intermittent hypoxia, an emerging therapeutic tool for inducing respiratory plasticity will also be introduced. A focus on emerging evidence and future work underscores the common goal to continue to improve survival for patients living with ALS.

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Section: Therapeutic Acute Intermittent Hypoxia (Taih)mentioning

confidence: 99%

Respiratory therapies for Amyotrophic Lateral Sclerosis: A state of the art review

et al. 2023

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“…Intermittent hypoxic training is a non-pharmacologic and systemic therapy that has a wide spectrum of beneficial effects against major diseases/disorders in humans, such as metabolic, cardiovascular, and neurodegenerative ailments. For example, intermittent hypoxic training resulted in augmentation of hypoxic sensitivity and significant decrease in blood concentration of DOPA in the patients with Parkinson’s disease [ 27 ], improved collective inspiratory muscle activity in patients with amyotrophic lateral sclerosis [ 28 ], increased cerebral blood flow in patients with heart failure [ 29 ], provided cardiovascular benefits in elderly people [ 30 ], decreased systolic blood pressure in patients with hypertension [ 31 , 32 ], upregulated erythropoietin [ 33 , 34 ], improved cognitive performance and quality of life in old people [ 35 ], alleviated surgery trauma [ 36 ], diminished oxidative stress [ 37 ], and normalized blood insulin levels in pre-diabetic patients [ 38 ]. Nevertheless, some pathological forms of intermittent hypoxia, e.g., severe obstructive sleep apnea (OSA), may induce destructive consequences in the body, including mitochondrial dysregulation, acidosis, altered mitochondrial membrane permeability, and impaired ATP biosynthesis [ 39 ], leading to impairment in attention, memory, and executive function and acceleration of AD development, along with cardiovascular injuries [ 40 ].…”

Section: Introductionmentioning

confidence: 99%

Response of Circulating Inflammatory Markers to Intermittent Hypoxia-Hyperoxia Training in Healthy Elderly People and Patients with Mild Cognitive Impairment

Serebrovska

Tumanovska

et al. 2022

Life

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Intermittent hypoxia-hyperoxia training (IHHT) is a non-pharmacological therapeutic modality for management of some chronic- and age-related pathologies, such as Alzheimer’s disease (AD). Our previous studies demonstrated significant improvement of cognitive function after IHHT in the patients with mild cognitive impairment (MCI). The present study further investigated the effects of IHHT on pro-inflammatory factors in healthy elderly individuals and patients with early signs of AD. Twenty-nine subjects (13 healthy subjects without signs of cognitive impairment syndrome and 16 patients diagnosed with MCI; age 52 to 76 years) were divided into four groups: Healthy+Sham (n = 7), Healthy+IHHT (n = 6), MCI+Sham (n = 6), and MCI+IHHT (n = 10). IHHT was carried out 5 days per week for 3 weeks (total 15 sessions), and each daily session included 4 cycles of 5-min hypoxia (12% FIO2) and 3-min hyperoxia (33% FIO2). Decline in cognitive function indices was observed initially in both MCI+Sham and MCI+IHHT groups. The sham training did not alter any of the parameters, whereas IHHT resulted in improvement in latency of cognitive evoked potentials, along with elevation in APP110, GDF15 expression, and MMP9 activity in both healthy subjects and those with MCI. Increased MMP2 activity, HMGB1, and P-selectin expression and decreased NETs formation and Aβ expression were also observed in the MCI+IHHT group. There was a negative correlation between MoCA score and the plasma GDF15 expression (R = −0.5799, p < 0.05) before the initiation of IHHT. The enhanced expression of GDF15 was also associated with longer latency of the event-related potentials P330 and N200 (R = 0.6263, p < 0.05 and R = 0.5715, p < 0.05, respectively). In conclusion, IHHT upregulated circulating levels of some inflammatory markers, which may represent potential triggers for cellular adaptive reprogramming, leading to therapeutic effects against cognitive dysfunction and neuropathological changes during progression of AD. Further investigation is needed to clarify if there is a causative relationship between the improved cognitive function and the elevated inflammatory markers following IHHT.

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“…hand/arm and leg/walking function) 2,3 . Beyond it’s physiological relevance, repetitive AIH exposure is emerging as a promising therapeutic modality to improve breathing, walking and arm/hand function in people with chronic spinal cord injury 1,4,5 and ALS 6 . However, greater understanding of mechanisms underlying AIH-induced motor plasticity is essential to optimize its application for therapeutic benefit 3 .…”

Section: Introductionmentioning

confidence: 99%

Daily fluctuations in spinal adenosine determine mechanisms of respiratory motor plasticity

Marciante

Seven

Kelly

et al. 2022

Preprint

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Plasticity is a fundamental property of the neural system controlling breathing. One key example of respiratory motor plasticity is phrenic long-term facilitation (pLTF), a prolonged increase in phrenic nerve activity following intermittent exposure to low oxygen (acute intermittent hypoxia, AIH). pLTF arises from distinct intracellular signaling cascades initiated by serotonin and adenosine, respectively, that interact via powerful crosstalk inhibition. We demonstrate serotonin versus adenosine balance varies dramatically with time-of-day and the specific AIH protocol. The fundamental mechanism driving pLTF shifts from serotonin-dominant, adenosine-constrained during rest, to adenosine-dominant, serotonin-constrained in the active phase using our standard AIH protocol. This mechanistic flip results from both daily changes in basal spinal adenosine levels across time-of-day and hypoxia-evoked adenosine release. Since AIH is emerging as a promising therapeutic modality to restore respiratory and non-respiratory movements in people with spinal injury and ALS, new knowledge that time-of-day and protocol impact pLTF mechanisms has experimental, biological and translational implications.

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Acute intermittent hypoxia and respiratory muscle recruitment in people with amyotrophic lateral sclerosis: A preliminary study

Cited by 22 publications

References 86 publications

Respiratory therapies for Amyotrophic Lateral Sclerosis: A state of the art review

Respiratory therapies for Amyotrophic Lateral Sclerosis: A state of the art review

Response of Circulating Inflammatory Markers to Intermittent Hypoxia-Hyperoxia Training in Healthy Elderly People and Patients with Mild Cognitive Impairment

Daily fluctuations in spinal adenosine determine mechanisms of respiratory motor plasticity

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