Spinal activation of the cAMP-PKA pathway induces respiratory motor recovery following high cervical spinal cord injury. 2008

S Kajana, and H G Goshgarian
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, 540 East Canfield, Detroit, MI 48201, USA.

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.

UI MeSH Term Description Entries
D007839 Functional Laterality Behavioral manifestations of cerebral dominance in which there is preferential use and superior functioning of either the left or the right side, as in the preferred use of the right hand or right foot. Ambidexterity,Behavioral Laterality,Handedness,Laterality of Motor Control,Mirror Writing,Laterality, Behavioral,Laterality, Functional,Mirror Writings,Motor Control Laterality,Writing, Mirror,Writings, Mirror
D008297 Male Males
D010791 Phrenic Nerve The motor nerve of the diaphragm. The phrenic nerve fibers originate in the cervical spinal column (mostly C4) and travel through the cervical plexus to the diaphragm. Nerve, Phrenic,Nerves, Phrenic,Phrenic Nerves
D012143 Respiratory Physiological Phenomena Physiological processes and properties of the RESPIRATORY SYSTEM as a whole or of any of its parts. Respiratory Physiologic Processes,Respiratory Physiological Processes,Respiratory Physiology,Physiology, Respiratory,Pulmonary Physiological Phenomena,Pulmonary Physiological Phenomenon,Pulmonary Physiological Process,Pulmonary Physiological Processes,Respiratory Physiological Concepts,Respiratory Physiological Phenomenon,Respiratory Physiological Process,Concept, Respiratory Physiological,Concepts, Respiratory Physiological,Phenomena, Pulmonary Physiological,Phenomena, Respiratory Physiological,Phenomenas, Pulmonary Physiological,Phenomenas, Respiratory Physiological,Phenomenon, Pulmonary Physiological,Phenomenon, Respiratory Physiological,Phenomenons, Pulmonary Physiological,Phenomenons, Respiratory Physiological,Physiologic Processes, Respiratory,Physiological Concept, Respiratory,Physiological Concepts, Respiratory,Physiological Phenomena, Pulmonary,Physiological Phenomena, Respiratory,Physiological Phenomenas, Pulmonary,Physiological Phenomenas, Respiratory,Physiological Phenomenon, Pulmonary,Physiological Phenomenon, Respiratory,Physiological Phenomenons, Pulmonary,Physiological Phenomenons, Respiratory,Physiological Process, Pulmonary,Physiological Process, Respiratory,Physiological Processes, Pulmonary,Physiological Processes, Respiratory,Process, Pulmonary Physiological,Process, Respiratory Physiological,Processes, Pulmonary Physiological,Pulmonary Physiological Phenomenas,Pulmonary Physiological Phenomenons,Respiratory Physiological Concept,Respiratory Physiological Phenomenas,Respiratory Physiological Phenomenons
D002245 Carbon Dioxide A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. Carbonic Anhydride,Anhydride, Carbonic,Dioxide, Carbon
D002574 Cervical Vertebrae The first seven VERTEBRAE of the SPINAL COLUMN, which correspond to the VERTEBRAE of the NECK. Cervical Spine,Cervical Spines,Spine, Cervical,Vertebrae, Cervical
D003627 Data Interpretation, Statistical Application of statistical procedures to analyze specific observed or assumed facts from a particular study. Data Analysis, Statistical,Data Interpretations, Statistical,Interpretation, Statistical Data,Statistical Data Analysis,Statistical Data Interpretation,Analyses, Statistical Data,Analysis, Statistical Data,Data Analyses, Statistical,Interpretations, Statistical Data,Statistical Data Analyses,Statistical Data Interpretations
D004594 Electrophysiology The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic

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