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. 2009 Oct 30:2:18.
doi: 10.3389/neuro.02.018.2009. eCollection 2009.

Shedding light on restoring respiratory function after spinal cord injury

Warren J Alilain  1 , Jerry Silver
Affiliations

Shedding light on restoring respiratory function after spinal cord injury

Warren J Alilain et al. Front Mol Neurosci. .

Abstract

Loss of respiratory function is one of the leading causes of death following spinal cord injury. Because of this, much work has been done in studying ways to restore respiratory function following spinal cord injury (SCI) - including pharmacological and regeneration strategies. 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. In this article we briefly review the history of various attempts to restore breathing after C2 hemisection, and focus on our recent work using the activation of light sensitive channels to restore respiratory function after experimental SCI. 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.

Keywords: C2 hemisection; channelrhodopsin; optogenetics; phrenic nucleus; plasticity; regeneration; respiration; spinal cord injury.

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Figures

Figure 1
Figure 1
A diagram of the respiratory pathways to the spinal cord. The phrenic nuclei are located bilaterally in the caudal C3 to rostral C6 spinal cord. The excitatory inspiratory drive comes from the rostral ventral respiratory group located in the medulla. Axons from the RVRG can decussate in the medulla to bilaterally innervate the phrenic nuclei. C2 hemisection (black bar) results in unilateral disruption of RVRG-spinal pathways (red lines) and quiescence of the ipsilateral phrenic nerve leading to paralysis of the ipsilateral hemidiaphragm. The crossed phrenic pathway (dashed lines) can circumvent the C2 hemisection by descending contralateral to the lesion and crossing over near the level of the phrenic nuclei. Normally inactive, activation of this spared pathway can restore function. It has been recently shown that spinal interneurons may play a role in this pathway.
See this image and copyright information in PMC

References

    1. Alilain W. J., Goshgarian H. G. (2007). MK-801 upregulates NR2A protein levels and induces functional recovery of the ipsilateral hemidiaphragm following acute C2 hemisection in adult rats. J. Spinal Cord Med. 30, 346–354 - PMC - PubMed
    1. Alilain W. J., Goshgarian H. G. (2008). Glutamate receptor plasticity and activity-regulated cytoskeletal associated protein regulation in the phrenic motor nucleus may mediate spontaneous recovery of the hemidiaphragm following chronic cervical spinal cord injury. Exp. Neurol. 212, 348–35710.1016/j.expneurol.2008.04.017 - DOI - PMC - PubMed
    1. Alilain W. J., Horn K. P., Dick T. E., Silver J. (2006). Chondroitinase ABC-induced reduction of chondroitin sulfate proteoglycans and the perineuronal net following C2 hemisection. Program No. 720.7. Neuroscience Meeting Planner Atlanta, GA Soc. Neurosci., Online.
    1. Alilain W. J., Horn K. P., Dick T. E., Silver J. (2007). Chondroitinase ABC treatment following C2 hemisection results in dramatically enhanced ipsilateral hemi-diaphragmatic recovery. Program No. 137.4. Neuroscience Meeting Planner San Diego, CA Soc. Neurosci., Online.
    1. Alilain W. J., Li X., Horn K. P., Dhingra R., Dick T. E., Herlitze S., Silver J. (2008). Light-induced rescue of breathing after spinal cord injury. J. Neurosci. 28, 11862–1187010.1523/JNEUROSCI.3378-08.2008 - DOI - PMC - PubMed