RNA interference for CFTR attenuates lung fluid absorption at birth in rats.
Female; Pregnancy; Rats; Genes; Cells; Animal Population Groups; Animal Studies; Lung; Respiratory Mucosa; Genes – Drug Effects; Biological Transport – Drug Effects; Lung – Drug Effects; Lung – Metabolism; Membrane Proteins – Metabolism; Respiratory Mucosa – Drug Effects; Respiratory Mucosa – Metabolism; RNA – Metabolism; RNA – Pharmacodynamics; Water – Metabolism
Background: Small interfering RNA (siRNA) against αENaC (α-subunit of the epithelial Na channel) and CFTR (cystic fibrosis transmembrane conductance regulator) was used to explore ENaC and CTFR function in newborn rat lungs. Methods: Twenty-four hours after trans-thoracic intrapulmonary (ttip) injection of siRNAgenerating plasmid DNA (pSi-0, pSi-4, or pSi-C2), we measured CFTR and ENaC expression, extravascular lung water, and mortality. Results: αENaC and CFTR mRNA and protein decreased by \textasciitilde80% and \textasciitilde85%, respectively, following αENaC and CFTR silencing. Extravascular lung water and mortality increased after αENaC and CFTR-silencing. In pSi-C2-transfected isolated DLE cells there were attenuated CFTR mRNA and protein. In pSi-4-transfected DLE cells αENaC mRNA and protein were both reduced. Interestingly, CFTR-silencing also reduced αENaC mRNA and protein. αENaC silencing, on the other hand, only slightly reduced CFTR mRNA and protein. Conclusion: Thus, ENaC and CFTR are both involved in the fluid secretion to absorption conversion around at birth.
Li T; Koshy S; Folkesson H G
Respiratory research
2008
2008-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1186/1465-9921-9-55" target="_blank" rel="noreferrer noopener">10.1186/1465-9921-9-55</a>
Maturation of the Coordination Between Respiration and Deglutition with and Without Recurrent Laryngeal Nerve Lesion in an Animal Model.
*Animal model; *Deglutition; *Development; *Infant; *Recurrent laryngeal nerve; *Respiration; *Sensorimotor; Animal; Animal Population Groups; Animals; Biological; Deglutition – Physiology; Deglutition Disorders; Deglutition/*physiology; Disease Models; Humans; Laryngeal Nerves – Injuries; Laryngeal Nerves – Physiology; Larynx – Physiology; Larynx/*physiology; Models; Newborn; Questionnaires; Recurrent Laryngeal Nerve Injuries/*complications; Recurrent Laryngeal Nerve/physiology; Respiration; Swine
The timing of the occurrence of a swallow in a respiratory cycle is critical for safe swallowing, and changes with infant development. Infants with damage to the recurrent laryngeal nerve, which receives sensory information from the larynx and supplies the intrinsic muscles of the larynx, experience a significant incidence of dysphagia. Using our validated infant pig model, we determined the interaction between this nerve damage and the coordination between respiration and swallowing during postnatal development. We recorded 23 infant pigs at two ages (neonatal and older, pre-weaning) feeding on milk with barium using simultaneous high-speed videofluoroscopy and measurements of thoracic movement. With a complete linear model, we tested for changes with maturation, and whether these changes are the same in control and lesioned individuals. We found (1) the timing of swallowing and respiration coordination changes with maturation; (2) no overall effect of RLN lesion on the timing of coordination, but (3) a greater magnitude of maturational change occurs with RLN injury. We also determined that animals with no surgical intervention did not differ from animals that had surgery for marker placement and a sham procedure for nerve lesion. The coordination between respiration and swallowing changes in normal, intact individuals to provide increased airway protection prior to weaning. Further, in animals with an RLN lesion, the maturation process has a larger effect. Finally, these results suggest a high level of brainstem sensorimotor interactions with respect to these two functions.
Ballester Ashley; Gould Francois; Bond Laura; Stricklen Bethany; Ohlemacher Jocelyn; Gross Andrew; DeLozier Katherine R; Buddington Randall; Buddington Karyl; Danos Nicole; German Rebecca
Dysphagia
2018
2018-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s00455-018-9881-z" target="_blank" rel="noreferrer noopener">10.1007/s00455-018-9881-z</a>
LVC Timing in Infant Pig Swallowing and the Effect of Safe Swallowing.
*Animal model; *Aspiration; *Deglutition; *Deglutition disorders; *Dysphagia; *Infant; *Laryngeal vestibule closure; *Recurrent laryngeal nerve; Animal; Animal Population Groups; Animals; Aspiration – Etiology; Aspiration/*etiology; Biological; Deglutition – Physiology; Deglutition Disorders – Etiology; Deglutition Disorders/*etiology; Deglutition/*physiology; Disease Models; Humans; Laryngeal Nerve Injuries/*complications; Laryngeal Nerves – Injuries; Larynx; Models; Newborn; Oropharynx; Pneumonia; Questionnaires; Swine
Recurrent laryngeal nerve (RLN) injury in neonates, a complication of head and neck surgeries, leads to increased aspiration risk and swallowing dysfunction. The severity of resulting sequelae range from morbidity, such as aspiration pneumonia, to mortality from infection and failure to thrive. The timing of airway protective events including laryngeal vestibule closure (LVC) is implicated in aspiration. We unilaterally transected the RLN in an infant pig model to observe changes in the timing of swallowing kinematics with lesion and aspiration. We recorded swallows using high-speed video-fluoroscopic swallow studies (VFSS) and scored them using the Infant Mammalian Penetration and Aspiration Scale (IMPAS). We hypothesized that changes would occur in swallowing kinematics (1) between RLN lesion and control animals, and (2) among safe swallows (IMPAS 1), penetration swallows (IMPAS 3), and aspiration swallows (IMPAS 7). We observed numerous changes in timing following RLN lesion in safe and unsafe swallows, suggesting pervasive changes in the coordination of oropharyngeal function. The timing of LVC, posterior tongue, and hyoid movements differed between pre- and post-lesion in safe swallows. Posterior tongue kinematics differed for post-lesion swallows with penetration. The timing and duration of LVC and posterior tongue movement differed between aspiration swallows pre- and post-lesion. After lesion, safe swallows and swallows with aspiration differed in timing of LVC, laryngeal vestibule opening, and posterior tongue and hyoid movements. The timing of thyrohyoid muscle activity varied with IMPAS, but not lesion. Further study into the pathophysiology of RLN lesion-induced swallowing dysfunction is important to developing novel therapies.
Gross Andrew; Ohlemacher Jocelyn; German Rebecca; Gould Francois
Dysphagia
2018
2018-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s00455-017-9832-0" target="_blank" rel="noreferrer noopener">10.1007/s00455-017-9832-0</a>