Effects of Breathing Mild Bouts of Low Oxygen on Limb Mobility After Spinal Injury

Accumulating evidence suggests that repeatedly breathing low oxygen levels for brief periods
(termed intermittent hypoxia) is a safe and effective treatment strategy to promote
meaningful functional recovery in persons with chronic spinal cord injury. Repetitive
exposure to mild hypoxia triggers a cascade of events in the spinal cord, including new
protein synthesis and increased sensitivity in the circuitry necessary for breathing and
walking. Recently, the investigators demonstrated that daily (5 consecutive days of)
intermittent hypoxia stimulated walking enhancement in persons with chronic spinal cord
injury.

Despite these exciting findings, important questions remain. First, does intermittent hypoxia
improve walking recovery by increasing strength or muscle coordination or both? Understanding
its mechanisms will allow us to best apply intermittent hypoxia in the clinic. Second,
initial studies indicate that the beneficial effects of intermittent hypoxia are greatest
when intermittent hypoxia is used just prior to task training and that the benefits are
greatest for the practiced task. The investigators will explore this possibility by examining
the effects of intermittent hypoxia on walking ability and force production when applied
alone and when applied in combination with walking training or strength training. The
investigators expect to observe the greatest improvements in walking ability in those
individuals receiving intermittent hypoxia with walking training and the greatest
improvements in strength in response to intermittent hypoxia with strength training. Third,
studies suggest that intermittent hypoxia induces spinal plasticity by increasing the
expression of a key plasticity-promoting protein, brain-derived neurotrophic factor (BDNF).
Mutations in the BDNF gene have been shown to impair BDNF functionality. Thus, the
investigators will also explore the impact of BDNF polymorphisms on responsiveness to
intermittent hypoxia therapy.

Inclusion Criteria:

- Age 18 and 75 years (the latter to reduce likelihood of heart disease)

- Medical clearance to participate

- Lesion at or below C2 and above T12 with non-progressive etiology

- Classified as motor-incomplete with visible volitional leg movement

- Injury greater than 1 year

Exclusion Criteria:

- Concurrent severe medical illness (i.e., infection, cardiovascular disease,
ossification, recurrent autonomic dysreflexia, unhealed decubiti, and history of
pulmonary complications)

- Pregnant women because of the unknown affects of AIH on pregnant women and fetus

- History of seizures, brain injury, and/or epilepsy

- Undergoing concurrent physical therapy

- Diabetes

- Cirrhosis

- Caffeine and/or NSAID allergies or intolerances