Chronic Intermittent Hypoxia-Induced Neuroinflammation Undermines Respiratory Motor Plasticity After Chronic Incomplete Cervical Spinal Cord Injury
Technical Report,01 Jul 2018,30 Jun 2019
University of Florida Gainesville United States
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The goal of this project is to determine the impact of chronic intermittent hypoxia, a primary feature of sleep apnea, on respiratory recovery and plasticity following chronic cervical spinal cord injury SCI. Prior work has shown that chronic intermittent hypoxia can trigger neuroinflammation and impair expression of respiratory plasticity. This this work has important clinical applications in SCI, since the prevalence of sleep apnea is much higher in than the uninjured population. Thus it raises concern that individuals with chronic SCI who also suffer from sleep apnea may have limited potential for plasticity and recovery of breathing function, if underlying inflammation is not addressed. Major accomplishments from this reporting period include 1 obtaining institutional approvals 2 recruitment and training of study personnel, which resulted in completion of a related preliminary study which showed dose-dependence effects of intermittent hypoxia on expression of respiratory plasticity and markers of spinal neuroinflammation and 3 completion of spinal injury and sham surgeries and subsequent aging of animals to a chronic post-surgical time point required for aim 1. Terminal neurophysiology and tissue processing for aim 1 are planned for the early part of the upcoming reporting cycle. Work from this first year provides the first direct evidence of a dose effect of intermittent hypoxia, which ranges from therapeutic at low doses, to pathologic at higher doses. Upcoming studies are the first assessments of high-dose, chronic intermittent hypoxia on respiratory plasticity and recovery of phrenic output in chronic spinal cord injury. Success of this project can lead to a significant paradigm shift in current approaches to managing respiratory dysfunction after SCI.
- Anatomy and Physiology