Developmental changes in brainstem neurons regulating lower airway caliber.

Premature infants are at risk for lower airway obstruction; however, maturation of reflex pathways regulating lower airway patency is inadequately studied. We hypothesized that postnatal maturation causes developmental change in brainstem efferent airway-related vagal preganglionic neurons (AVPNs) within the rostral nucleus ambiguus (rNA) that project to the airways, and in pulmonary afferent fibers that terminate in the nucleus tractus solitarius (NTS). Ferrets aged 7, 14, 21 and 42 days received intrapulmonary injection of Cholera toxin β subunit (CT-b), a transganglionic retrograde tracer. Five days later, their brainstem was processed for dual immunolabeling of CT-b and the cholinergic marker, choline acetyl transferase (ChAT). CT-b labeled AVPNs and CT-b labeled afferent fiber optical density were analyzed. There was a significantly higher CT-b labeled cell number within the rNA at the youngest compared to older ages. All efferent CT-b labeled cells expressed ChAT. Optical density of CT-b labeled afferent fibers was also higher at 7 compared to 14 days. We conclude that the number of efferent AVPNs and afferent fiber optical density both diminish over the second postnatal week. We speculate that exposure to injurious agents in early postnatal life may inhibit natural remodeling and thereby enhance later vulnerability to airway hyperreactivity.