title: Spinal cord injury-induced plasticity in the mouse--the crossed phrenic phenomenon.
abstract: The crossed phrenic phenomenon (CPP) describes respiratory functional plasticity that arises following spinal cord injury. Cervical spinal cord hemisection rostral to the phrenic nucleus paralyzes the ipsilateral hemidiaphragm by interrupting the descending flow of respiratory impulses from the medulla to phrenic motoneurons in the spinal cord. This loss of activity converts some synapses on phrenic motoneurons from a "functionally ineffective" state pre-hemisection to a "functionally latent" state post-hemisection. If the animal is subjected to respiratory stress by transecting the contralateral phrenic nerve, this latent respiratory pathway is activated and function is restored to the paralyzed hemidiaphragm. The mechanisms underlying this plasticity are not well-defined, particularly at the molecular level. Therefore, we explored whether it was possible to demonstrate the CPP in mice, a species amenable to a molecular genetic approach. We show the CPP qualitatively in mice using electromyographic (EMG) recordings from the diaphragm. Interestingly, our data also suggest that in the mouse latent fibers in the ventral funiculus ipsilateral to an anatomically incomplete hemisection may also play a role in the CPP. In particular, we examined the inter-operative delay time between the spinal cord injury and contralateral phrenicotomy required for a response. As the inter-operative delay was reduced, the proportion of mice displaying the CPP decreased from 95% for overnight animals, 86% in 4-8 h, to 77% for 1-2 h mice, and less than 28% for animals receiving a phrenicotomy under 0.5 h post-spinal cord lesion. This is the first study to demonstrate the CPP in mice.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Denver, 80262, USA.
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Minor
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Akison
authors.forename: Harry G
authors.initials: HG
authors.lastname: Goshgarian
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Seeds
mesh_terms: D000818:Animals; D017763:Autonomic Denervation / Q000379:methods; D003964:Diaphragm / Q000503:physiopathology; D004195:Disease Models, Animal; D004576:Electromyography / Q000379:methods; D007839:Functional Laterality; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000502:physiology*; D010791:Phrenic Nerve / Q000293:injuries / Q000503:physiopathology*; D015656:Respiratory Mechanics / Q000502:physiology; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors