Genetic Biomarkers of Intermittent Hypoxia-Induced Respiratory Motor Plasticity in Chronic SCI

Abstract

Background: Spinal cord injury (SCI) disrupts neural pathways to respiratory motor neurons, diminishing breathing capacity and airway defense (e.g., cough). Indeed, respiratory impairment is a leading cause of lung infection, rehospitalization and death after SCI. There is a critical need for new strategies to restore breathing ability and airway defense in people living with chronic SCI. Acute intermittent hypoxia (AIH) repetitive exposure to brief episodes of low inspired oxygen is a promising new strategy to restore breathing capacity by promoting spinal neuroplasticity. Exciting outcomes in nine SCI trials demonstrate that AIH improves human respiratory and limb function. Unfortunately, ~40% of individuals exhibit minimal response to AIH, making it crucial to optimize AIH protocols to maximize functional benefits and identify genetic biomarkers distinguishing those most/least likely to benefit from AIH-based treatments. An essential goal of our proposed study is to optimize AIH-based treatments by 1) combining hypoxia with hypercapnia (5% inspired CO2)during each episode (AIHH) to augment respiratory motor plasticity; and 2) combining AIHH with an established form of task-specific training (respiratory strength training). Genetic biomarkers for the efficacy of AIH have not yet been established but are vital to advance AIH-based treatment towards phase 3 clinical trials.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2023
Accession Number
AD1226596

Entities

People

  • Emily J Fox
  • Gordon Mitchell

Organizations

  • University of Florida

Tags

Readers

  • Cardiovascular Physiology
  • Neurotrauma and Rehabilitation Medicine.

Technology Areas

  • Biotechnology