Chorioamnionitis induces enteric nervous system injury: Effects of timing and inflammation in the ovine fetus

Background Chorioamnionitis, inflammation of the chorion and amnion, which often results from intrauterine infection, is associated with premature birth and contributes to significant neonatal morbidity and mortality, including necrotizing enterocolitis (NEC). Recently, we have shown that chronic chorioamnionitis is associated with significant structural enteric nervous system (ENS) abnormalities that may predispose to later NEC development. Understanding time point specific effects of an intra-amniotic (IA) infection on the ENS is important for further understanding the pathophysiological processes and for finding a window for optimal therapeutic strategies for an individual patient. The aim of this study was therefore to gain insight in the longitudinal effects of intrauterine LPS exposure (ranging from 5 h to 15 days before premature delivery) on the intestinal mucosa, submucosa, and ENS in fetal lambs by use of a well-established translational ovine chorioamnionitis model. Methods We used an ovine chorioamnionitis model to assess outcomes of the fetal ileal mucosa, submucosa and ENS following IA exposure to one dose of 10 mg LPS for 5, 12 or 24 h or 2, 4, 8 or 15 days. Results Four days of IA LPS exposure causes a decreased PGP9.5- and S100β-positive surface area in the myenteric plexus along with submucosal and mucosal intestinal inflammation that coincided with systemic inflammation. These changes were preceded by a glial cell reaction with early systemic and local gut inflammation. ENS changes and inflammation recovered 15 days after the IA LPS exposure. Conclusions The pattern of mucosal and submucosal inflammation, and ENS alterations in the fetus changed over time following IA LPS exposure. Although ENS damage seemed to recover after prolonged IA LPS exposure, additional postnatal inflammatory exposure, which a premature is likely to encounter, may further harm the ENS and influence functional outcome. In this context, 4 to 8 days of IA LPS exposure may form a period of increased ENS vulnerability and a potential window for optimal therapeutic strategies

Corrigendum: Chronic Intra-Uterine Ureaplasma parvum infection induces injury of the enteric Nervous System in Ovine Fetuses

Michael L. Beeton was not included as an author in the published article. The corrected Author Contributions Statement appears below

The role of angiotensin II and prostaglandins in arcade formation in a developing microvascular network

There are basically two types of branching patterns in the terminal part of the arteriolar tree. On the one hand, in a number of tissues, including the developing chick embryo chorioallantoic membrane (CAM), the pattern is dichotomous, whereas in other tissues many arteriolar-arteriolar connections, arcades, are found. The structure of the branching pattern depends on the local physical and chemical environment. The goal of this study was to investigate whether substances with an effect on vascular growth influence the vascular branching pattern. We treated chick embryo CAMs daily from day 7 to day 14 postfertilization with 0.9% NaCl, angiotensin II (ANG-II), ANG-II in combination with different angiotensin receptor subtype antagonists, i.e., losartan and CGP 42112A, or the prostaglandin synthesis inhibitor acetylsalicylic acid (ASA). Arcade formation was quantified by counting the number of arcades per cm2 treated area, the branch-node ratio and mean surface area of arcade loops. ANG-II caused a 2-fold increase in the number of arcades versus 0.9% NaCl. Addition of ASA or losartan caused a further enhancement of arcade formation expressed in the number and branch-node ratio. CGP 42112A had no significant effect on arcade formation. From these data we hypothesize that ANG-II stimulates the process of capillary upgrading to arterioles by stimulation of arteriolar smooth muscle cell growth. Prostaglandins normally counteract this effect. After blockade of prostaglandin action, the ANG-II-induced arterialization is enhanced, resulting in pronounced arcade formation. The actions of losartan may be related to its inhibitory effects on prostaglandins rather than angiotensin receptor antagonism