Acute Intermittent Hypoxia on Leg Function Following Spinal Cord Injury

Repetitive Exposure of Intermittent Hypoxia to Enhance Walking Recovery in Persons With Chronic Spinal Cord Injury

The purpose of this study is to determine how the nervous system controlling leg muscles is altered following spinal cord injury and how they may be affected by brief periods of low oxygen inhalation over time.

The investigators hypothesize:

• Acute intermittent hypoxia (AIH) exposure will increase maximum voluntary leg strength in persons with incomplete cervical spinal cord injury (SCI)
• AIH exposure will increase multijoint reflex excitability of leg muscles in persons with incomplete cervical SCI
• AIH exposure will increase walking performance in persons with incomplete cervical SCI

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 C2---L5 with non---progressive etiology;
• >6 months since SCI to ensure minimal confounds of spontaneous neurological recovery;
• those classified as ambulatory must have the 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