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Diaphragmatic recovery in rats with cervical spinal cord injury induced by a theophylline nanoconjugate: Challenges for clinical use
- Source :
- J Spinal Cord Med
- Publication Year :
- 2019
- Publisher :
- Taylor & Francis, 2019.
-
Abstract
- Context: Following a spinal cord hemisection at the second cervical segment the ipsilateral hemidiaphragm is paralyzed due to the disruption of the rostral ventral respiratory group (rVRG) axons descending to the ipsilateral phrenic motoneurons (PN). Systemically administered theophylline activates a functionally latent crossed phrenic pathway (CPP) which decussates caudal to the hemisection and activates phrenic motoneurons ipsilateral to the hemisection. The result is return of function to the paralyzed hemidiaphragm. Unfortunately, in humans, systemically administered theophylline at a therapeutic dose produces many unwanted side effects. Design and setting: A tripartite nanoconjugate was synthesized in which theophylline was coupled to a neuronal tracer, wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), using gold nanoparticles as the coupler. Following intradiaphragmatic injection of the nanoconjugate, WGA-HRP selectively targets the theophylline-bound nanoconjugate to phrenic motoneurons initially, followed by neurons in the rVRG by retrograde transsynaptic transport. Participants: (N/A) Interventions: (N/A) Outcome Measures: Immunostaining, Electromyography (EMG). Results: Delivery of the theophylline-coupled nanoconjugate to the nuclei involved in respiration induces a return of respiratory activity as detected by EMG of the diaphragm and a modest return of phrenic nerve activity. Conclusion: In addition to the modest return of phrenic nerve activity, there were many difficulties using the theophylline nanoconjugate because of its chemical instability, which suggests that the theophylline nanoconjugate should not be developed for clinical use as explained herein.
- Subjects :
- Ventral respiratory group
Diaphragm
Pyramidal Tracts
Metal Nanoparticles
Context (language use)
02 engineering and technology
Nanoconjugates
03 medical and health sciences
Theophylline
medicine
Animals
Spinal cord injury
Research Articles
Spinal Cord Injuries
030304 developmental biology
Phrenic nerve
Motor Neurons
0303 health sciences
Medulla Oblongata
business.industry
Electromyography
Cervical Cord
Recovery of Function
021001 nanoscience & nanotechnology
medicine.disease
musculoskeletal system
Wheat germ agglutinin
Diaphragm (structural system)
Rats
Phrenic Nerve
Disease Models, Animal
medicine.anatomical_structure
nervous system
Anesthesia
Neurology (clinical)
Gold
0210 nano-technology
business
Immunostaining
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- J Spinal Cord Med
- Accession number :
- edsair.doi.dedup.....d167393bfa6658d288cffd81db8403c9