Abstract
Intermittent hypoxia treatment (IH) has been shown to improve respiratory function in both pre-clinical animal models and human subjects following spinal cord injury (SCI), historically consisting of alternating and equal intervals of hypoxic and normoxic exposure. We describe such a procedure as fixed duration IH (FD-IH) and modulation of its severity, intermittency, and post-injury time-point of application differentially affects expression of breathing motor plasticity. As such, the established IH protocol exhibits similarity to instrumental conditioning and can be described as behavioral training through reinforcement. Findings from the field of operant conditioning, a form of more advanced learning, inspire the consideration that FD-IH protocols may be improved through exchanging fixed for varied durations of hypoxia between reinforcement. Thus, we hypothesized that varied duration intermittent hypoxia treatment (VD-IH) would induce greater breathing motor recovery ipsilateral to injury than FD-IH after cervical SCI in rats. To test this hypothesis, we treated animals with VD-IH or FD-IH for 5 days at 1 week and at 8 weeks following cervical SCI, then assessed breathing motor output by diaphragm electromyography (EMG) recording, and compared between groups. At 1 week post-injury, VD-IH-exposed animals trended slightly toward exhibiting greater levels of respiratory recovery in the hemidiaphragm ipsilateral to lesion than did FD-IH-treated animals, but at 8 weeks FD-IH produced significantly greater respiratory motor output than did VD-IH. Thus, these results identify a novel sensitivity of respiratory motor function to variations in the IH protocol that may lead to development of more effective treatments following SCI.
Highlights
The majority of spinal cord injuries (SCIs) in the human population occur at the cervical level and can result in devastating respiratory motor dysfunction including diaphragm paresis and paralysis.[1]
FD-Intermittent hypoxia (IH) and varied duration intermittent hypoxia treatment (VD-IH) treatment at 1 week post-C2Hx does not induce differential respiratory motor activity Of those injured animals exposed to VD-IH treatment at 1 week post-C2Hx (n = 11), 1 was eliminated before analysis due to a dislodged electrode
Pattern sensitivity of IH treatment-induced long-term facilitation (LTF) The primary finding from this study suggests that FDIH treatment of rats at a chronic, 8-week time-point post-C2Hx produces higher amplitude of breathing motor recovery than treatment with our VD-IH paradigm at the same time-point following injury
Summary
The majority of spinal cord injuries (SCIs) in the human population occur at the cervical level and can result in devastating respiratory motor dysfunction including diaphragm paresis and paralysis.[1]. Intermittent hypoxia (IH) treatment has been experimentally applied in a rodent model of unilateral cervical SCI termed a C2 hemisection (C2Hx) to activate spared and typically latent pathways through episodically heightening the subjects’ respiratory drive and increasing serotonergic signaling This leads to a prolonged increase in their phrenic motor output known as long-term facilitation (LTF).[4,5] Following experimental SCI, LTF can manifest in recovery of breathing motor function in the paralyzed hemidiaphragm, depending on various factors that include the duration, number, and post-injury time-point of IH treatment(s).[5,6,7] at 12 weeks following C2Hx in rats, IH alone does not effectively induce breathing motor recovery.[8] Even when IH is combined with treatment that degrades plasticity-inhibiting components of the extracellular matrix, breathing motor outcome is varied, and initially includes subjects with tonic diaphragmatic activity alongside those exhibiting coordinated inspiratory motor function.[8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
