Effects of acute intermittent hypoxia on hand use after spinal cord trauma

Trumbower, Randy D.; Hayes, Heather B.; Mitchell, Gordon S.; Wolf, Steven L.; Stahl, Victoria A.

doi:10.1212/wnl.0000000000004596

Cited by 67 publications

(40 citation statements)

References 8 publications

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“…Furthermore, such results suggest uncovering how inflammation impacts the neural control of breathing is fundamental to understand changes in respiratory function during pathological conditions. Furthermore, for respiratory motor plasticity to be used clinically (21,45,46), we must also understand the interaction between plasticity and inflammation, which is common in many pathologies.…”

Section: Discussionmentioning

confidence: 99%

IL-1 receptor activation undermines respiratory motor plasticity after systemic inflammation

Hocker

Huxtable

2018

Journal of Applied Physiology

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Inflammation undermines respiratory motor plasticity, yet we are just beginning to understand the inflammatory signaling involved. Because interleukin-1 (IL-1) signaling promotes or inhibits plasticity in other central nervous system regions, we tested the following hypotheses: 1) IL-1 receptor (IL-1R) activation after systemic inflammation is necessary to undermine phrenic long-term facilitation (pLTF), a model of respiratory motor plasticity induced by acute intermittent hypoxia (AIH), and 2) spinal IL-1β is sufficient to undermine pLTF. pLTF is significantly reduced 24 h after lipopolysaccharide (LPS; 100 μg/kg ip, 12 ± 18%, n = 5) compared with control (57 ± 25%, n = 6) and restored by peripheral IL-1R antagonism (63 ± 13%, n = 5, AF-12198, 0.5 mg/kg ip, 24 h). Furthermore, acute, spinal IL-1R antagonism (1 mM AF-12198, 15 μl it) restored pLTF (53 ± 15%, n = 4) compared with LPS-treated rats (11 ± 10%; n = 5), demonstrating IL-1R activation is necessary to undermine pLTF after systemic inflammation. However, in healthy animals, pLTF persisted after spinal, exogenous recombinant rat IL-1β (rIL-1β) (1 ng ± AIH; 66 ± 26%, n = 3, 10 ng ± AIH; 102 ± 49%, n = 4, 100 ng + AIH; 93 ± 51%, n = 3, 300 ng ± AIH; 37 ± 40%, n = 3; P < 0.05 from baseline). In the absence of AIH, spinal rIL-1β induced progressive, dose-dependent phrenic amplitude facilitation (1 ng; -3 ± 5%, n = 3, 10 ng; 8 ± 22%, n = 3, 100 ng; 31 ± 12%, P < 0.05, n = 4, 300 ng; 51 ± 17%, P < 0.01 from baseline, n = 4). In sum, IL-1R activation, both systemically and spinally, undermines pLTF after LPS-induced systemic inflammation, but IL-1R activation is not sufficient to abolish plasticity. Understanding the inflammatory signaling inhibiting respiratory plasticity is crucial to developing treatment strategies utilizing respiratory plasticity to promote breathing during ventilatory control disorders. NEW & NOTEWORTHY This study gives novel insights concerning mechanisms by which systemic inflammation undermines respiratory motor plasticity. We demonstrate that interleukin-1 signaling, both peripherally and centrally, undermines respiratory motor plasticity. However, acute, exogenous interleukin-1 signaling is not sufficient to undermine respiratory motor plasticity.

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Section: Discussionmentioning

confidence: 99%

IL-1 receptor activation undermines respiratory motor plasticity after systemic inflammation

Hocker

Huxtable

2018

Journal of Applied Physiology

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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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“…Recently, the use of repeated daily mild intermittent hypoxia has been endorsed as a stand-alone or adjunct therapy to promote the recovery of respiratory and limb motor dysfunction (Trumbower et al 2012, Tester et al 2014aNavarrete-Opazo et al 2017a,b;Trumbower et al 2017). Our results showed that exposure to mild forms of intermittent hypoxia increases loop gain and the arousal threshold that could lead to increases in apnoea frequency and duration in individuals with obstructive sleep apnoea.…”

Section: Translational Significancementioning

confidence: 48%

“…, b ; Trumbower et al . ). Our results showed that exposure to mild forms of intermittent hypoxia increases loop gain and the arousal threshold that could lead to increases in apnoea frequency and duration in individuals with obstructive sleep apnoea.…”

Section: Discussionmentioning

confidence: 97%

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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Effects of acute intermittent hypoxia on hand use after spinal cord trauma

Abstract: NCT01272336.

Cited by 67 publications

References 8 publications

IL-1 receptor activation undermines respiratory motor plasticity after systemic inflammation

IL-1 receptor activation undermines respiratory motor plasticity after systemic inflammation

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

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

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