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  4. Shedding light on restoring respiratory function after spinal cord injury

Shedding light on restoring respiratory function after spinal cord injury

Frontiers in Molecular Neuroscience, 2009 · DOI: 10.3389/neuro.02.018.2009 · Published: October 30, 2009

Spinal Cord InjuryPulmonologyNeurology

Simple Explanation

Trauma at the cervical level is one of the most common types of spinal cord injury (SCI). Injuries at this level are particularly devastating since this results in disruption of the bulbospinal projections to the phrenic nucleus (PN), which is composed of motor neurons that directly innervate the diaphragm. In the laboratory, the model of choice for investigating cervical SCI and its resulting respiratory defi cits has been the C2 hemisection. In this model the cervical SC is exposed and hemisected from the midline all the way to the lateral most aspect of the cord. With the emergence of new and powerful tools from molecular neuroscience, new therapeutically relevant alternatives to these approaches have become available, including expression of light sensitive proteins called channelrhodopsins.

Study Duration
Not specified
Participants
Rats with C2 hemisection
Evidence Level
Review Article

Key Findings

  • 1
    Pharmacological intervention which can increase central respiratory drive might be a potential way to induce recovery of the ipsilateral hemidiaphragm following C2 hemisection – without contralateral phrenicotomy.
  • 2
    Following expression in both mammalian and non-mammalian tissue, it can be induced by photostimulation to depolarize neurons, fi re action potentials and control activity of neurons independent of any kind of pre-synaptic input
  • 3
    After restoring breathing activity with long light stimulation and then allowing the animal to recover for 1 day, we found that restored diaphragm function persisted for at least 24 h.

Research Summary

Loss of respiratory function is one of the leading causes of death following spinal cord injury. With the emergence of new and powerful tools from molecular neuroscience, new therapeutically relevant alternatives to these approaches have become available, including expression of light sensitive proteins called channelrhodopsins. We also discuss how such light-induced activity can help shed light on the inner workings of the central nervous system respiratory circuitry that controls diaphragmatic function.

Practical Implications

Pharmacological Interventions

Pharmacological interventions aimed at increasing central respiratory drive could potentially induce recovery of the ipsilateral hemidiaphragm following C2 hemisection without contralateral phrenicotomy.

Optogenetic Stimulation

Light-activated channelrhodopsins can be used to depolarize neurons and restore muscle activity independent of pre-synaptic input, offering a powerful means to activate quiescent cells and restore muscle function after SCI.

Spinal Respiratory Plasticity

The discovery of spinal respiratory plasticity and adaptation opens new avenues for therapeutic interventions, suggesting that spinal cord networks can be remodeled to restore function after SCI.

Study Limitations

  • 1
    Barriers to regeneration, such as the glial scar and inhibitory proteoglycans, limit the regeneration and sprouting of injured axons.
  • 2
    System-wide alterations caused by pharmacotherapy and environmental changes can have deleterious effects beyond the spinal cord.
  • 3
    The anatomical substrate mediating crossed communication between the two sides of the spinal cord remains unknown.

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