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Systemic administration of rolipram increases medullary and spinal cAMP and activates a latent respiratory motor pathway after high cervical spinal cord injury. J Spinal Cord Med 2009;32(2):175-82

Date

07/03/2009

Pubmed ID

19569465

Pubmed Central ID

PMC2678289

DOI

10.1080/10790268.2009.11760769

Scopus ID

2-s2.0-66449106384   24 Citations

Abstract

BACKGROUND/OBJECTIVE: High cervical spinal cord hemisection interrupts descending respiratory drive from the rostral ventral respiratory group in the medulla to the ipsilateral phrenic motoneurons. Hemisection results in the paralysis of the ipsilateral hemidiaphragm. Chronic administration of rolipram, a specific phosphodiesterase-IV inhibitor, promotes synaptic plasticity and restores phrenic nerve function after a high cervical spinal cord lesion. Here, we test the hypothesis that an acute administration of rolipram will increase spinal and medullary levels of 3',5'-cyclic adenosine monophosphate (cAMP) and induce phrenic nerve recovery after cervical (C2) spinal cord hemisection.

METHODS: Male Sprague-Dawley rats were subjected to left C2 hemisection surgery 1 week before experimentation. Bilateral phrenic nerve activity was recorded in anesthetized, vagotomized, and pancuronium paralyzed rats, and rolipram was intravenously applied (2 mg/kg).

RESULTS: Intravenous administration of rolipram increased phrenic nerve output in uninjured control and left C2 spinal cord-hemisected rats. In addition, rolipram restored respiratory-related activity to the left phrenic nerve made quiescent by the hemisection. In both uninjured and hemisected rats, rolipram significantly enhanced phrenic inspiratory burst amplitude and burst area compared with predrug values. Also, rolipram concomitantly increased spinal and medullary cAMP.

CONCLUSIONS: These results suggest that a phosphodiesterase inhibitor capable of elevating cAMP levels can enhance phrenic nerve output and restore respiratory-related phrenic nerve function after high cervical spinal cord injury. Thus, targeting the cAMP signaling cascade can be a useful therapeutic approach in promoting synaptic efficacy and respiratory recovery after cervical 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
Cervical Vertebrae
Cyclic AMP
Disease Models, Animal
Functional Laterality
Injections, Intravenous
Male
Phosphodiesterase Inhibitors
Phrenic Nerve
Rats
Rats, Sprague-Dawley
Respiration
Respiratory Center
Rolipram
Spinal Cord Injuries