Chronic Intermittent Hypoxia-Induced Neuroinflammation Undermines Respiratory Motor Plasticity After Chronic Incomplete Cervical Spinal Cord Injury
Abstract
One of the greatest problems faced by people with spinal cord injuries at the neck is an impaired ability to breathe independently. Oftentimes, these individuals require the assistance of a breathing machine to sustain life. Long-term dependence on breathing machines can lead to reduced quality of life and significantly increase the chances of sustaining life-threatening lung infections. Despite major advances in the medical management of spinal cord injuries, breathing dysfunction is the leading cause of death after injury. Therefore, the development of safe and effective therapies to restore breathing function is a major priority. Over the past few years, we have developed a novel method of restoring breathing capacity after spinal cord injury: repeated exposure to low levels of oxygen (known as acute intermittent hypoxia). We have recently discovered that several factors may undermine the benefits of acute intermittent hypoxia, limiting the potential for this treatment to help improve breathing function in people with spinal cord injury. One factor that may blunt the therapeutic response to acute intermittent hypoxia is inflammation, such as the inflammation of the spinal cord that results from chronic exposure to intermittent hypoxia. Importantly, chronic exposure to intermittent hypoxia (e.g., ?high-doses? intermittent hypoxia) is one of the major consequences of sleep disordered breathing (also known as sleep apnea), a condition that very common in people with spinal cord injuries. We do not yet know how chronic intermittent hypoxia caused by sleep apnea impacts the response to acute intermittent hypoxia in people who have spinal cord injuries, but based on or prior research and exciting preliminary results, we suspect that it will cause inflammation and will limit the positive effects that have been shown with this promising therapeutic strategy. In addition, we believe that we can treat this inflammation and restore the potential for acute intermittent hypoxia to improve breathing function in people with spinal cord injury. If true, the results of these studies may be very important, since something as simple as giving a person an anti-inflammatory pill prior to initiating therapy may improve the potential for the success of that therapy. Furthermore, the acute intermittent hypoxia is a therapy that has already been shown to be a safe and effective strategy for improving motor function in humans with spinal cord injuries, and several of the drugs being tested in the proposed studies have versions that are either currently approved for use in humans or are currently in development for other disorders. Thus, the results of the proposed experiments have a very real potential to translate into clinical use. The funding requested here is to complete our preliminary efforts so that we will be able to determine if these highly novel ideas are correct and useful. Although the project proposed here focuses on how chronic intermittent hypoxia caused by sleep apnea impacts recovery of breathing function, we strongly suspect that the lessons learned here will be of importance to other motor functions such as limb strength and coordination (including walking).
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710315
Entities
People
- Elisa Gonzalez-rothi
Organizations
- United States Army
- University of Florida