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  • The Role of the Crossed Phrenic Pathway after Cervical Contusion Injury and a New Model to Evaluate Therapeutic Interventions

    Final Number:

    Basem I Awad MD; Philippa M Warren PhD; Michael P. Steinmetz MD; Warren J. Alilain Ph.D.

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2013 Annual Meeting

    Introduction: Cervical spinal cord injuries are usually resulting in damage to the descending bulbospinal inspiratory tracts and phrenic motor neurons. A common deficit observed in the new contusion animal models is the inability to increase diaphragmatic activity in the face of respiratory challenge. In this report we tested the hypothesis that, following cervical contusion, all remaining tracts to the phrenic nucleus are active, including the crossed phrenic pathway (CPP). Additionally, we investigated the potential function these spared tracts might possess after injury.

    Methods: One week following a left C3/4 spinal hemi-contusion, bilateral diaphragm electromyographic recordings were taken and rats were randomly sub-grouped into three groups. The first group underwent a left C2 hemisection (LC2H) followed by contralateral phrenicotomy (n=6). The second group underwent contralateral phrenicotomy first, followed by LC2H (n=6). The third group received a right C2 hemisection(n=6).

    Results: In the first group, we find that eliminating the normal ipsilateral inspiratory tracts to the phrenic nucleus, through a LC2H rostral to the contusion, results in cessation of all hemidiaphragmatic activity on the side of the contusion and hemisection. While, performing a contralateral phrenicotomy restores some ipsilateral hemidiaphragmatic activity. In the second group, a phrenicotomy contralateral to the contusion was performed prior to a LC2H. This results in augmented ipsilateral hemidiaphragmatic activity. Additionally, after performing a more rostral LC2H hemidiaphragmatic activity still remained. However, in the third group, contralateral C2 hemisection results in a cessation of all hemidiaphragmatic activity ipsilateral to the contusion.

    Conclusions: Following a C3/4 hemi-contusion, not all tracts to the ipsilateral phrenic nucleus, in particular the CPP, are actively depolarizing phrenic motor neurons. Upon activation, the CPP can augment respiratory motor activity. Finally, this model of hemi-contusion and post contra-hemisection can be used to test potential therapies with greater accuracy and clinical relevance than cervical contusion models currently allow.

    Patient Care: Spinal cord injury at the cervical level usually resulted in the impaired ability to breathe. A mechanical ventilator is regularly needed to help these patients survive. However, this drastic intervention severely diminishes their quality of life, as well as increases their demands for extensive health care. Therefore, exploring ways to restore respiratory motor function following cervical SCI holds great clinical importance and relevance.

    Learning Objectives: By the conclusion of this session, participants should be able to know that: 1) After a high cervical hemicontusion the crossed phrenic pathway (CPP) is not actively depolarizing ipsilateral phrenic motor neurons. 2) Activation of the CPP after hemicontusion increases ipsilateral respiratory motor output. 3) Contralateral C2 hemisection eliminates respiratory motor output ipsilateral to a hemicontusion, suggesting a modulatory role for the CPP. 4) We generated a new model to assess therapeutic strategies after cervical contusion injuries.


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