Chorioamnionitis decreases neonatal respiratory pattern variability in transverse rat brainstem slices

Abstract

Chorioamnionitis is a major cause of perinatal inflammation and infection, and has been implicated in brain morbidity associated with preterm birth. Apnea of prematurity is a common clinical manifestation of neonatal inflammation suggesting that chorioamnionitis has a direct effect on the development of central respiratory output which is detectable using non‐linear analyses. We modeled chorioamnionitis by injecting 150 μg/kg of lipopolysaccharide (LPS) into the chorion space in alternate sacs (30 μl/sac) of pregnant Sprague Dawley dams (E16). Following normal birth of the pups, on the second postnatal day, we cut 500 μm transverse brainstem slices from LPS exposed and sham pups and recorded fictive inspiratory output from the hypoglossal nerve (XII) rootlet at both 5 and 8mM external [K+]. We analyzed the XII signal to quantify burst duration, interburst interval, and area of XII burst. We found no effect of prenatal LPS exposure on Te, Ti, frequency or coefficient of variation at either K+ concentration. However, the histogram entropy of the interburst intervals (a measure of variability), was significantly lower at 5mM K+ in LPS exposed pups (3.5±1.3) than shams (5.08±0.7). This suggests that endotoxin exposure in prenatal life impairs inspiratory pattern generation and such abnormalities could lead to ventilatory abnormalities in postnatal life.