Daily acute, but not chronic, intermittent hypoxia enhances phrenic motor plasticity in chronic cervical spinal cord injury
Abstract
Daily acute intermittent hypoxia (dAIH; 3–15 hypoxic episodes per day) is a promising therapeutic strategy to improve respiratory function after incomplete spinal cord injury by inducing spinal respiratory motor plasticity. Conversely, chronic intermittent hypoxia (CIH; >100 episodes per day) elicits multisystem pathology and is a hallmark of moderate sleep apnea, a condition highly prevalent in individuals with cervical spinal injury. In intact rats, 7 days of dAIH preconditioning enhances phrenic motor facilitation whereas it is abolished by 7 days of CIH, an effect likely due to CIH‐induced neuroinflammation. Since the impact of prolonged CIH (> 1 wk) or dAIH on the capacity for phrenic motor facilitation with chronic spinal cord injury has not been explored, we compared the effect of 28 days of normoxia (21% O2; 8hrs/day), dAIH (10, 5 min episodes of 10.5% O2 with 5 min normoxic intervals/day) or CIH (2 min hypoxic episodes with 2 min intervals; 8 hrs/day) on phrenic output in rats with chronic C2 spinal hemisection (C2Hx). Neurophysiology experiments were conducted one day after the final hypoxic exposure; bilateral phrenic nerve activity and moderate AIH‐induced phrenic long‐term facilitation (pLTF) were assessed. Ipsilateral phrenic nerve activity during baseline conditions and maximal chemoreflex activation was: 1) reduced in all injury groups vs intact rats (p0.94 and p>0.98, respectively). No group differences in contralateral phrenic nerve activity were observed in either condition (p>0.49 and p>0.18, respectively). dAIH enhanced ipsilateral pLTF vs. all other groups (p=0.01); in contrast, CIH had no effect on pLTF (p=0.43). In conclusion, neither dAIH nor CIH had any detectable impact on phrenic nerve activity in rats with chronic C2Hx, but dAIH enhanced the capacity for additional pLTF. Further work is needed to explore: 1) mechanisms of enhanced respiratory plasticity following dAIH; 2) if detrimental effects of CIH can be resolved by treatments that mitigate inflammation; and 3) how enhanced/restored phrenic motor plasticity can be harnessed to improve breathing ability in individuals with chronic cervical spinal cord injury.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2019
- Source ID
- 10.1096/fasebj.2019.33.1_supplement.731.6
Entities
People
- Alec Simon
- Arash Tadjalli
- Ashley Holland
- Ashley J. Ross
- Elisa J. Gonzalez‐rothi
- Gordon S. Mitchell
- Juliet Santiago
- Kelsey Stefan
- Kristin Smith
- Latoya L Allen
- Marissa C. Ciesla
- Mohamad El‐chami
- Zachary Asa
Organizations
- National Institutes of Health
- United States Department of Defense
- University of Florida