Daily acute intermittent hypoxia improves breathing function with acute and chronic spinal injury via distinct mechanisms

B. J. Dougherty, J. Terada, S. R. Springborn, S. Vinit, P. M. MacFarlane, G. S. Mitchell

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Daily acute intermittent hypoxia (dAIH) elicits respiratory plasticity, enhancing respiratory motor output and restoring breathing capacity after incomplete cervical spinal injuries (cSCI). We hypothesized that dAIH-induced functional recovery of breathing capacity would occur after both acute (2 weeks) and chronic (8 weeks) cSCI, but through distinct cellular mechanisms. Specifically, we hypothesized that dAIH-induced breathing recovery would occur through serotonin-independent mechanisms 2wks post C2 cervical hemisection (C2Hs), versus serotonin-dependent mechanisms 8wks post C2Hs. In two independent studies, dAIH or sham (normoxia) was initiated 1 week (Study 1) or 7 weeks (Study 2) post-C2Hs to test our hypothesis. Rats were pre-treated with intra-peritoneal vehicle or methysergide, a broad-spectrum serotonin receptor antagonist, to determine the role of serotonin signaling in dAIH-induced functional recovery. Our data support the hypothesis that dAIH-induced recovery of breathing capacity transitions from a serotonin-independent mechanism with acute C2Hs to a serotonin-dependent mechanism with chronic C2Hs. An understanding of shifting mechanisms giving rise to dAIH-induced respiratory motor plasticity is vital for clinical translation of dAIH as a therapeutic modality.

Original languageEnglish (US)
Pages (from-to)50-57
Number of pages8
JournalRespiratory Physiology and Neurobiology
StatePublished - Oct 2018

Bibliographical note

Funding Information:
Support for this work was provided by grants from: The National Institute of Health (NIH) 5RO1HL069064 (GSM), The Craig H. Neilsen Foundation (BJD, SV) and The Francis Family Foundation (PMM).

Publisher Copyright:
© 2017 Elsevier B.V.


  • Adenosine
  • Intermittent hypoxia
  • Long-term facilitation
  • Phrenic
  • Plasticity
  • Serotonin
  • Spinal cord injury


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