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

绒毛膜羊膜炎诱发肠道神经系统损伤:时间和炎症对绵羊胎儿的影响

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作者:C Heymans, I H de Lange, K Lenaerts, L C G A Kessels, M Hadfoune, G Rademakers, V Melotte, W Boesmans, B W Kramer, A H Jobe, M Saito, M W Kemp, W G van Gemert, T G A M Wolfs

Background

Chorioamnionitis, inflammation of the chorion and amnion, which often

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.

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.

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