Repetitive intermittent hypoxia induces respiratory and somatic motor recovery after chronic cervical spinal injury

Mary R. Lovett-Barr, Irawan Satriotomo, Gillian D. Muir, Julia E R Wilkerson, Michael S. Hoffman, Stéphane Vinit, Gordon S. Mitchell

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Spinal injury disrupts connections between the brain and spinal cord, causing life-long paralysis. Most spinal injuries are incomplete, leaving spared neural pathways to motor neurons that initiate and coordinate movement. One therapeutic strategy to induce functional motor recovery is to harness plasticity in these spared neural pathways. Chronic intermittent hypoxia (CIH) (72 episodes per night, 7 nights) increases synaptic strength in crossed spinal synaptic pathways to phrenic motoneurons below aC2 spinal hemisection. However, CIH also causes morbidity (e.g., high blood pressure, hippocampal apoptosis), rendering it unsuitable as a therapeutic approach to chronic spinal injury. Less severe protocols of repetitive acute intermittent hypoxia may elicit plasticity without associated morbidity. Here we demonstrate that daily acute intermittent hypoxia (dAIH; 10 episodes per day, 7 d) induces motor plasticity in respiratory and nonrespiratory motor behaviors without evidence for associated morbidity. dAIH induces plasticity in spared, spinal pathways to respiratory and nonrespiratory motor neurons, improving respiratory and nonrespiratory (forelimb) motor function in rats with chronic cervical injuries. Functional improvements were persistent and were mirrored by neurochemical changes in proteins that contribute to respiratory motor plasticity after intermittent hypoxia (BDNF and TrkB) within both respiratory and nonrespiratory motor nuclei. Collectively, these studies demonstrate that repetitive acute intermittent hypoxia may be an effective and non-invasive means of improving function in multiple motor systems after chronic spinal injury.

Original languageEnglish (US)
Pages (from-to)3591-3600
Number of pages10
JournalJournal of Neuroscience
Volume32
Issue number11
DOIs
StatePublished - Mar 14 2012

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Spinal Injuries
Motor Neurons
Neural Pathways
Morbidity
Forelimb
Brain-Derived Neurotrophic Factor
Diaphragm
Paralysis
Hypoxia
Spinal Cord
Apoptosis
Hypertension
Wounds and Injuries
Brain
Therapeutics
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Lovett-Barr, M. R., Satriotomo, I., Muir, G. D., Wilkerson, J. E. R., Hoffman, M. S., Vinit, S., & Mitchell, G. S. (2012). Repetitive intermittent hypoxia induces respiratory and somatic motor recovery after chronic cervical spinal injury. Journal of Neuroscience, 32(11), 3591-3600. https://doi.org/10.1523/JNEUROSCI.2908-11.2012

Repetitive intermittent hypoxia induces respiratory and somatic motor recovery after chronic cervical spinal injury. / Lovett-Barr, Mary R.; Satriotomo, Irawan; Muir, Gillian D.; Wilkerson, Julia E R; Hoffman, Michael S.; Vinit, Stéphane; Mitchell, Gordon S.

In: Journal of Neuroscience, Vol. 32, No. 11, 14.03.2012, p. 3591-3600.

Research output: Contribution to journalArticle

Lovett-Barr, MR, Satriotomo, I, Muir, GD, Wilkerson, JER, Hoffman, MS, Vinit, S & Mitchell, GS 2012, 'Repetitive intermittent hypoxia induces respiratory and somatic motor recovery after chronic cervical spinal injury', Journal of Neuroscience, vol. 32, no. 11, pp. 3591-3600. https://doi.org/10.1523/JNEUROSCI.2908-11.2012
Lovett-Barr, Mary R. ; Satriotomo, Irawan ; Muir, Gillian D. ; Wilkerson, Julia E R ; Hoffman, Michael S. ; Vinit, Stéphane ; Mitchell, Gordon S. / Repetitive intermittent hypoxia induces respiratory and somatic motor recovery after chronic cervical spinal injury. In: Journal of Neuroscience. 2012 ; Vol. 32, No. 11. pp. 3591-3600.
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