Unexpected Benefits of Intermittent Hypoxia: Enhanced Respiratory and Nonrespiratory Motor Function

Intermittent hypoxia (IH) is most often thought of for its role in morbidity associated with sleep-disordered breathing, including central nervous system pathology. However, recent evidence suggests that the nervous system fights back in an attempt to minimize pathology by increasing the expression of growth/trophic factors that confer neuroprotection and neuroplasticity. For example, even modest ("low dose") IH elicits respiratory motor plasticity, increasing the strength of respiratory contractions and breathing. These low IH doses upregulate hypoxia-sensitive growth/trophic factors within respiratory motoneurons but do not elicit detectable pathologies such as hippocampal cell death, neuroinflammation, or systemic hypertension. Recent advances have been made toward understanding cellular mechanisms giving rise to IH-induced respiratory plasticity, and attempts have been made to harness the benefits of low-dose IH to treat respiratory insufficiency after cervical spinal injury. Our recent realization that IH also upregulates growth/trophic factors in nonrespiratory motoneurons and improves limb (or leg) function after incomplete chronic spinal injuries suggests that IH-induced plasticity is a general feature of motor systems. Collectively, available evidence suggests that low-dose IH may represent a safe and effective treatment to restore lost motor function in diverse clinical disorders that impair motor function.