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Nanoconjugate-bound adenosine A 1 receptor antagonist enhances recovery of breathing following acute cervical spinal cord injury
- Source :
- Experimental Neurology. 292:56-62
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Respiratory complications in patients with spinal cord injury (SCI) are common and can have a negative impact on the quality of patients' lives. Previously, we found that intradiaphragmatic administration of the nanoconjugate-bound A1 adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) induced recovery of diaphragm function following SCI in rats. When administered immediately following the injury, recovery was observed as early as 3days following SCI and it persisted until the end of the study, 28days after the drug delivery. The recovery was observed using diaphragmatic electromyography (EMG) as well as phrenic nerve recordings; both of which were conducted under anesthetized conditions. Confounding effects of anesthetic may make data interpretation complex in terms of the impact on overall ventilatory function and clinical relevance. The objective of the present study was to test the hypothesis that intradiaphragmatic administration of nanoconjugate-bound DPCPX, enhances recovery of ventilation following SCI in the unanesthetized rat. To that end, Sprague-Dawley rats underwent C2 spinal cord hemisection (C2Hx) on day 0 and received either: (i) 0.15μg/kg of nanoconjugate-bound DPCPX or (ii) vehicle control (50μl distilled water). To assess ventilation, unrestrained whole body plethysmography (WBP) was performed on day 0 (immediately before the surgery) and 3, 7, 14, 21 and 28days following the SCI. Frequency, tidal volume, and minute ventilation data were analyzed in two minute bins while the animal was calm and awake. We found that a single administration of the nanoconjugate-bound A1 adenosine receptor antagonist facilitated recovery of tidal volume and minute ventilation following SCI. Furthermore, the treatment attenuated SCI-associated increases in respiratory frequency. Taken together, this study suggests that the previously observed DPCPX nanoconjugate-induced recovery in diaphragmatic and phrenic motor outputs may translate to a clinically meaningful improvement in ventilatory function in patients with SCI.
- Subjects :
- 0301 basic medicine
business.industry
Diaphragmatic breathing
medicine.disease
Adenosine receptor antagonist
03 medical and health sciences
Adenosine A1 receptor
030104 developmental biology
0302 clinical medicine
Developmental Neuroscience
Neurology
Anesthesia
Breathing
Medicine
business
Spinal cord injury
030217 neurology & neurosurgery
Tidal volume
Respiratory minute volume
Phrenic nerve
Subjects
Details
- ISSN :
- 00144886
- Volume :
- 292
- Database :
- OpenAIRE
- Journal :
- Experimental Neurology
- Accession number :
- edsair.doi...........b77938f312a5feafcb8e39944b8fe2c4