IL-1 receptor blockade prevents fetal cortical brain injury but not preterm birth in a mouse model of inflammation-induced preterm birth and perinatal brain injury.
Am J Reprod Immunol
; 71(5): 418-26, 2014 May.
Article
em En
| MEDLINE
| ID: mdl-24592965
ABSTRACT
PROBLEM:
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)-1ß 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-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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lesões Encefálicas
/
Receptores de Interleucina-1
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Nascimento Prematuro
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Proteína Antagonista do Receptor de Interleucina 1
Idioma:
En
Revista:
Am J Reprod Immunol
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos