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Spinal activation of the cAMP-PKA pathway induces respiratory motor recovery following high cervical spinal cord injury. Brain Res 2008 Sep 26;1232:206-13

Date

07/29/2008

Pubmed ID

18656458

Pubmed Central ID

PMC2573999

DOI

10.1016/j.brainres.2008.07.012

Scopus ID

2-s2.0-51049089530   18 Citations

Abstract

The present study investigated the involvement of the adenosine 3'5'-cyclic monophosphate-dependent protein kinase A (cAMP-PKA) pathway in the activation of the crossed-phrenic pathways after left C2 spinal cord hemisection. Experiments were conducted on left C2 spinal cord hemisected, anesthetized, vagotomized, pancuronium paralyzed, and artificially ventilated male Sprague-Dawley rats. One week post-injury, the ipsilateral phrenic nerve exhibited no respiratory-related activity indicating a functionally complete hemisection. Intrathecal spinal cord administration of the cAMP analog, 8-Br-cAMP at the level of the phrenic nucleus resulted in an enhancement of contralateral phrenic nerve output and a restoration of respiratory-related activity in the phrenic nerve ipsilateral to the hemisection. Furthermore, pre-treatment with Rp-8-Br-cAMP, a PKA inhibitor, abolished the effects of 8-Br-cAMP. These results suggest that PKA activation is necessary for the cAMP-mediated respiratory recovery following high cervical spinal cord injury and that activation of intracellular signaling cascades may represent an important strategy for improving respiratory function after spinal cord injury.

Author List

Kajana S, Goshgarian HG

Author

Kajana Satkunendrarajah PhD Assistant Professor in the Neurosurgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Apnea
Carbon Dioxide
Cervical Vertebrae
Cyclic AMP
Cyclic AMP-Dependent Protein Kinases
Data Interpretation, Statistical
Electrophysiology
Enzyme Inhibitors
Functional Laterality
Male
Phrenic Nerve
Rats
Rats, Sprague-Dawley
Respiratory Physiological Phenomena
Signal Transduction
Spinal Cord
Spinal Cord Injuries
Thionucleotides