Document Detail


Early phrenic motor neuron loss and transient respiratory abnormalities after unilateral cervical spinal cord contusion.
MedLine Citation:
PMID:  23534670     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Contusion-type cervical spinal cord injury (SCI) is one of the most common forms of SCI observed in patients. In particular, injuries targeting the C3-C5 region affect the pool of phrenic motor neurons (PhMNs) that innervates the diaphragm, resulting in significant and often chronic respiratory dysfunction. Using a previously described rat model of unilateral midcervical C4 contusion with the Infinite Horizon Impactor, we have characterized the early time course of PhMN degeneration and consequent respiratory deficits following injury, as this knowledge is important for designing relevant treatment strategies targeting protection and plasticity of PhMN circuitry. PhMN loss (48% of the ipsilateral pool) occurred almost entirely during the first 24 h post-injury, resulting in persistent phrenic nerve axonal degeneration and denervation at the diaphragm neuromuscular junction (NMJ). Reduced diaphragm compound muscle action potential amplitudes following phrenic nerve stimulation were observed as early as the first day post-injury (30% of pre-injury maximum amplitude), with slow functional improvement over time that was associated with partial reinnervation at the diaphragm NMJ. Consistent with ipsilateral diaphragmatic compromise, the injury resulted in rapid, yet only transient, changes in overall ventilatory parameters measured via whole-body plethysmography, including increased respiratory rate, decreased tidal volume, and decreased peak inspiratory flow. Despite significant ipsilateral PhMN loss, the respiratory system has the capacity to quickly compensate for partially impaired hemidiaphragm function, suggesting that C4 hemicontusion in rats is a model of SCI that manifests subacute respiratory abnormalities. Collectively, these findings demonstrate significant and persistent diaphragm compromise in a clinically relevant model of midcervical contusion SCI; however, the therapeutic window for PhMN protection is restricted to early time points post-injury. On the contrary, preventing loss of innervation by PhMNs and/or inducing plasticity in spared PhMN axons at the diaphragm NMJ are relevant long-term targets.
Authors:
Charles Nicaise; David M Frank; Tamara J Hala; Michèle Authelet; Roland Pochet; Dominique Adriaens; Jean-Pierre Brion; Megan C Wright; Angelo C Lepore
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurotrauma     Volume:  30     ISSN:  1557-9042     ISO Abbreviation:  J. Neurotrauma     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-06-21     Completed Date:  2014-01-23     Revised Date:  2014-06-17    
Medline Journal Info:
Nlm Unique ID:  8811626     Medline TA:  J Neurotrauma     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1092-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cervical Vertebrae
Diaphragm / innervation*,  pathology
Disease Models, Animal
Female
Motor Neurons / pathology*
Phrenic Nerve / pathology*,  physiopathology
Rats
Rats, Sprague-Dawley
Recovery of Function / physiology
Respiration Disorders / etiology*,  pathology
Spinal Cord Injuries / complications*,  pathology,  physiopathology
Grant Support
ID/Acronym/Agency:
R01 NS079702/NS/NINDS NIH HHS
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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