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Daily acute, but not chronic, intermittent hypoxia enhances phrenic motor plasticity in chronic cervical spinal cord injury
Author(s) -
GonzalezRothi Elisa J,
Tadjalli Arash,
Allen Latoya L,
Ciesla Marissa C,
Simon Alec,
Asa Zachary,
Smith Kristin,
ElChami Mohamad,
Holland Ashley,
Santiago Juliet,
Stefan Kelsey,
Ross Ashley,
Mitchell Gordon S
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.731.6
Subject(s) - medicine , intermittent hypoxia , phrenic nerve , anesthesia , spinal cord injury , spinal cord , hypoxia (environmental) , apnea , respiratory system , obstructive sleep apnea , chemistry , organic chemistry , psychiatry , oxygen
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% O 2 ; 8hrs/day), dAIH (10, 5 min episodes of 10.5% O 2 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 C 2 spinal hemisection (C 2 Hx). 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 (p<0.0001 and p<0.009, respectively); and 2) unaffected by dAIH or CIH (p>0.94 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 C 2 Hx, 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. Support or Funding Information NIH: OT2OD023854, K12 HDO55929 (EGR), T32 HD055929 (LLA); Department of Defense: SCI160123 (EGR) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .