Protocol-Speciﬁc Effects of Intermittent Hypoxia Pre-Conditioning on Phrenic Motor Plasticity in Rats with Chronic Cervical Spinal Cord Injury

JOURNAL OF NEUROTRAUMA, 2021 · DOI: 10.1089/neu.2020.7324 · Published: May 1, 2021

Spinal Cord Injury Neurology Neuroplasticity

Simple Explanation

This study explores how different types of intermittent hypoxia (IH), a condition where oxygen levels fluctuate, affect breathing in rats with spinal cord injuries. The researchers compared low-dose daily acute intermittent hypoxia (dAIH) to high-dose chronic intermittent hypoxia (CIH). The main goal was to see if these IH protocols could improve phrenic nerve activity, which controls the diaphragm, a key muscle for breathing. They measured baseline phrenic nerve activity and how it responded to induced long-term potentiation (pLTF). The results showed that dAIH enhanced pLTF but didn't improve baseline phrenic output. CIH, unlike in previous studies with intact rats, didn't abolish pLTF in rats with chronic spinal cord injury.

Study Duration

28 days

Participants

42 adult male Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
Daily acute intermittent hypoxia (dAIH) enhanced phrenic long-term facilitation (pLTF) bilaterally in rats with chronic cervical spinal cord injury (cSCI) compared to those exposed to normoxia.
2
Chronic intermittent hypoxia (CIH) did not abolish pLTF in rats with chronic cSCI, unlike what was observed in shorter protocols with intact rats.
3
Neither dAIH nor CIH improved baseline phrenic motor output in rats with chronic cSCI.

Research Summary

This study compared the effects of prolonged daily acute intermittent hypoxia (dAIH) versus chronic intermittent hypoxia (CIH) on phrenic motor outcomes in rats with chronic cervical spinal cord injury (cSCI). dAIH enhanced phrenic motor plasticity (pLTF) but did not improve baseline phrenic output, while CIH did not abolish pLTF, contrary to what was expected from studies on intact rats. The findings suggest that the therapeutic efficacy of repetitive AIH may be undermined by unknown factors in rats with chronic spinal hemisection, and further research is needed to optimize AIH protocols for specific conditions such as chronic SCI.

Practical Implications

Clinical Trial Optimization

The study highlights the need for additional protocol optimization before dAIH can be harnessed for therapeutic benefit in individuals with chronic spinal cord injury.

Understanding Respiratory Plasticity

The research contributes to a deepening understanding that respiratory plasticity and functional recovery after prolonged IH are dose-dependent.

Task-Specific Training

dAIH may be most effective when paired with task-specific training, in this case, repeated activation of the phrenic motor circuit.

Study Limitations

1
Unknown factor(s) undermine the therapeutic efficacy of repetitive AIH in rats with chronic (vs. acute) spinal hemisection, such as adenosine 2A receptor activation, age, or chronic inflammation.
2
The model of CIH employed in the present study does not faithfully mimic the lived experience of a person with sleep-disordered breathing.
3
The injured spinal cord has been referred to as a 'new' spinal cord, meaning that biological responses after spinal injury may be quite distinct from intact animals.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury