Spinal activation of the cAMP-PKA pathway induces respiratory motor recovery following high cervical spinal cord injury.
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.
Kajana
S
S
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, 540 East Canfield, Detroit, MI 48201, USA.
Goshgarian
H G
HG
D000818:Animals; D001049:Apnea / Q000139:chemically induced / Q000503:physiopathology; D002245:Carbon Dioxide / Q000494:pharmacology; D002574:Cervical Vertebrae / Q000293:injuries*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D003627:Data Interpretation, Statistical; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D008297:Male; D010791:Phrenic Nerve / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012143:Respiratory Physiological Phenomena; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013873:Thionucleotides / Q000494:pharmacology
D004791:Enzyme Inhibitors; D013873:Thionucleotides; D002245:Carbon Dioxide; C016957:adenosine-3',5'-cyclic phosphorothioate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases