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UF Health University of Florida
Breathing Research and Therapeutics Center College of Public Health and Health Professions
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Mitchell Lab Research

The focus of the Mitchell laboratory concerns fundamental mechanisms of spinal neuroplasticity, particularly plasticity in the phrenic motor system elicited repetitive exposure to low oxygen, or acute intermittent hypoxia (AIH). Pioneering research concerning mechanisms of AIH-induced plasticity in the phrenic motor system has inspired new therapeutic strategies to improve both respiratory and non-respiratory motor impairment by applying AIH in rodent models and in humans with spinal cord injuries (SCI) and motor neuron disease (ALS). 

on image: Fundamental Neuroscience Using rats as an experimental model, AIH-induced phrenic motor plasticity is studied in physiological and pathological conditions to understand intracellular, inter-cellular, and neural network mechanisms of plasticity. Current efforts concern factors that regulate (amplify or undermine) AIH-induced plasticity, including repetitive AIH-preconditioning, AIH protocol, time-of-day, inflammation, genetics, age, and sex. Translation in Rodent Models We are attempting to harness AIH as a treatment to improve breathing in clinical disorders that most often end life due to respiratory failure. When therapeutic AIH is applied to rat models of cervical SCI and ALS, profound functional recovery of breathing capacity is observed. In collaboration with other laboratories across North America, we also apply AIH to improve limb function. Additional steps are needed to optimize AIH as a therapeutic modality by understanding factors that enhance or undermine its effectiveness. Translation in Humans Important collaborations advance human translation in several respects, including ongoing (funded) clinical trials to test the potential of therapeutic AIH to improve: 1) breathing function in people with chronic SCI and ALS; 2) airway defense, including swallowing/breathing coordination and cough; and 3) walking and arm/hand function.
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