Acute Intermittent Hypoxia on Leg Function Following Spinal Cord 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 clinical questions remain. For example, the
investigators do not know if prolonged, but less intense intermittent hypoxia induces
longer-lasting motor recovery as has been shown in rat models. The investigators hypothesize
that repetitive exposures to modest bouts of low oxygen will enhance and prolong walking
recovery in persons with chronic spinal cord injury. The investigators anticipate
intermittent hypoxia-induced improvements in overground walking ability, likely due to
greater balance in excitatory and inhibitory neural transmission. Whereas excitatory inputs
drive walking, inhibitory inputs sculpt and coordinate muscle activity; yet so often remain
compromised after chronic injury. Thus, the investigators also predict that repetitive
exposures to intermittent hypoxia will result in improved inhibition and subsequently enhance
muscle coordination during walking. The investigators will use multiple experimental
approaches, including muscle electromyography, measurements of walking dynamics and stretch
reflexes. Finally, it is critical to assure that repetitive exposures to intermittent hypoxia
do not elicit pathologies characteristic of more severe, chronic hypoxia experienced by
individuals with obstructive sleep apnea. The investigators will confirm that repetitive
exposure to mild bouts of intermittent hypoxia is safe.

Inclusion Criteria:

- 18 to 75 years old (the latter to reduce likelihood of heart disease);

- medically stable with clearance from physician to participate;

- motor--‐incomplete SCI at C4--‐T12 with non--‐progressive etiology;

- >1 year since SCI to ensure minimal confounds of spontaneous neurological recovery;

- ability to advance one step overground without human assistance.

Exclusion Criteria:

- concurrent illness, including unhealed decubiti, severe neuropathic or chronic pain
syndrome, infection, cardiovascular disease, osteoporosis (history of fractures),
active heterotopic ossification, or known history of peripheral nerve injury to legs;

- less than 24 on the Mini-mental Exam;

- recurrent autonomic dysreflexia

- cardiopulmonary complications

- concurrent physical therapy

- pregnancy because of unknown effects of AIH on a fetus, although women will not
otherwise be excluded