Intermittent Hypoxia-Induced Motor Plasticity in Sub-Acute Spinal Cord Injury

Summary

Spinal cord injury (SCI) disrupts neural pathways to respiratory motor neurons, diminishing breathing capacity and airway defense (e.g., cough). Indeed, respiratory impairment is a leading cause of infection, re-hospitalization and death after SCI. There is a critical need for new strategies to restore breathing ability and airway defense in people with SCI. Acute intermittent hypoxia (AIH) - repetitive exposure to brief episodes of low inspired oxygen - is a promising strategy to restore breathing capacity by promoting spinal neuroplasticity. Exciting outcomes in \>12 SCI trials completed to date demonstrate that AIH improves human respiratory and limb function. Unfortunately, \~40% of individuals exhibit minimal response to AIH, making it essential to 1) optimize AIH protocols to maximize functional benefits; and 2) identify genetic biomarkers distinguishing those most/least likely to benefit from AIH-based treatments. The purpose of the pilot study, to be conducted in a small sample of participants with sub-acute SCI (2 weeks to 6 months post injury), is to preliminarily compare the effects of two intermittent hypoxia protocols. Since AIH-induced plasticity may be induced via serotonin or adenosine-driven mechanisms and these pathways compete and inhibit each other, each protocol favors a distinct mechanistic pathway. Our long-term objective is to test the hypothesis that a longer duration (i.e., augmented) hypoxia protocol, favoring adenosine mechanisms, enhances respiratory motor plasticity more than an AIH protocol targeting serotonin mechanisms (low O2 + CO2) in people with sub-acute SCI. Since an individual's genetics can influence the response to rehabilitation, we are also investigating how certain genes are related to breathing changes after these treatments. Data acquired through this pilot study will be used to inform a larger, more definitive clinical trial and will contribute to estimations of the magnitude and direction of effects.

Description

Eligibility

Age range

18–70 years

Sex

All

Healthy volunteers

No

Interventions

• Other
  Augmented Acute Intermittent Hypoxia (aAIH)

  aAIH (augmented acute intermittent hypoxia) consists of 3, 5-minute episodes of low oxygen (9-13% O2), interspersed with 3-min room air intervals. Each study participant will complete 6 sessions of augmented AIH (aAIH), which consists of 3, 5-minute exposures. Each exposure involves a 5-minute hypoxic episode (9-13% inspired O2), with a 3-min interval of room air breathing (21% O2). Gas mixtures will be delivered via Douglas bags (pre-filled with desired gas mixture) that are coupled to a non-rebreathing valve and facemask. A manual-control valve allows seamless gas mixture switching. Participant safety will be continuously monitored in real-time using non-invasive sensors and LabChart software. For instance, inspired and expired concentrations of O2 will be monitored by continuous recordings of arterial O2 saturation and end-tidal gas, respectively. Furthermore, vital signs (respiratory rate, tidal volume, heart rate, and blood pressure) will be continuously monitored.

• Other
  Acute Intermittent Hypercapnic-Hypoxia (AIHH)

  AIHH consists of 1-min episodes of low oxygen (9% O2) and elevated carbon dioxide (5% CO2), interspersed with 1.5 min room air. Each participant will complete 6 sessions of AIHH exposure, which consists of 15, 1-minute hypercapnic hypoxic episodes (4-5% inspired CO2, 9-13% inspired O2), with 1.5-minute intervals of room air breathing (21% O2). Gas mixtures will be delivered in the same manner described for AIH intervention. Participant safety will be continuously monitored in real-time using LabChart software. For instance, inspired and expired concentrations of CO2 and O2 will be monitored by continuous recordings of arterial O2 saturation and end-tidal gas, respectively. Furthermore, vital signs (respiratory rate, heart rate, and blood pressure) will be monitored.

• Other
  Sham AIH

Location