In:
American Journal of Reproductive Immunology, Wiley, Vol. 71, No. 5 ( 2014-05), p. 418-426
Kurzfassung:
Exposure to intrauterine inflammation, associated with preterm birth, has been linked to a devastating spectrum of neurobehavioral disorders. Mechanisms of this injury are unknown. Using a mouse model of intrauterine inflammation, we have observed a disruption of fetal neuronal morphology along with a marked elevation of interleukin ( IL )‐1β in the fetal brain and placenta. In this study, we hypothesized that IL ‐1 plays a key role in perinatal brain injury. Method of study Utilizing a mouse model of inflammation‐induced preterm birth, we investigated the role of IL ‐1 in fetal cortical injury as well as preterm birth. In these studies, dams received systemic treatment with IL ‐1 receptor antagonist prior to administration of intrauterine inflammation. Results Systemic maternal antagonism of IL ‐1 improved fetal cortical neuronal injury associated with the exposure to intrauterine inflammation, without affecting the phenotype of preterm birth. IL ‐1 receptor antagonist blocked activation of neuronal nitric oxide synthase in perinatal cortex, a key enzyme implicated in neurotoxicity. Conclusion Our data suggest that fetal cortical brain injury and preterm birth may occur by divergent mechanisms. Furthermore, our studies indicate maternal administration of IL ‐1 receptor antagonist ( IL ‐1 RA ) blocked neuronal nitric oxide synthase activation observed in the brain cortex and, we speculate, that this alteration in activation leads to demonstrated decreased neurotoxicity.
Materialart:
Online-Ressource
ISSN:
1046-7408
,
1600-0897
DOI:
10.1111/aji.2014.71.issue-5
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2014
ZDB Id:
2024667-5
