Journal
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
Volume 71, Issue 5, Pages 418-426Publisher
WILEY
DOI: 10.1111/aji.12216
Keywords
IL-1 receptor antagonist; intrauterine inflammation; mouse model
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Funding
- ABOG/AAOGF Grant
- NICHD [K08HD073315]
- Passano Foundation Grant
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ProblemExposure 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)-1 in the fetal brain and placenta. In this study, we hypothesized that IL-1 plays a key role in perinatal brain injury. Method of studyUtilizing 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. ResultsSystemic 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. ConclusionOur 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-1RA) blocked neuronal nitric oxide synthase activation observed in the brain cortex and, we speculate, that this alteration in activation leads to demonstrated decreased neurotoxicity.
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